ANNUAL MEETING ABSTRACTS 157A (mean 3.6%, range 0.6 – 8.4%) and metastatic carcinoid tumor (mean 11.5%, range showed isolated loss of PMS2, one showed loss of MSH2 and MSH6, and one showed 1.3 – 46.7%) (p=0.0019). The survival time was much shorter in patients with metastatic loss of MLH1 and PMS2. The difference in the MMR loss rate by IHC between the carcinoid tumor (median survival 5.8 years) comparing to those with primary ovarian three groups approaches statistically significant (p= 0.065). carcinoid tumor (median 14.2 years) (p=0.0005). A strong association between Ki67 Conclusions: MMR IHC testing of CRCs has been well described; however, testing index and patient survival time was identified (Hazard ratio 1.11, p=0.001). of adenomas has only been described previously in limited fashion and when done has Conclusions: Comparing to primary ovarian carcinoid tumor, metastatic carcinoid tumor been enriched for patients with LS. Here we identified a propensity for polyps with usually exhibits a higher Ki67 index and a worse outcome. Ki67 index is significantly villous features from younger patients to display MMR IHC abnormalities. These results associated with the survival time in patients with carcinoid tumor involving ovary. suggest that MMR IHC testing of adenomas with villous features in patients less than 40 years old may assist with the identification of LS. Gastrointestinal Pathology 623 Clincopathologic Studies of PD-L1 Expression on Esophageal Adenocarcinoma and Squamous Cells Carcinoma Sohaib Abu-Farsakh, Amy Lalonde, Tongtong Wu, Zhongren Zhou. University of 621 Tubulovillous Adenomas with Serrated Features Are Precursors Rochester, Rochester, NY. to KRAS Mutant Colorectal Carcinoma Amrou Abdelkader, Christopher Hartley, Catherine Hagen. Medical College of Background: Programmed death ligand 1 (PD-L1) is a ligand for the inhibitory Wisconsin, Milwaukee, WI; University of Wisconsin Hospital and Clinics, Madison, WI. programmed death receptor 1 (PD-1). Induction of PD-L1 expression on tumor cells Background: Conventional adenomas and serrated polyps represent precursor lesions leads to the inhibition of immune responses against cancer. Therefore, blockage of to two separate pathways of colorectal carcinoma. Occasionally, tubulovillous adenomas PD-1 or PD-L1 can activate the anti-tumor activity. Our study investigated the PD-L1 (TVA) show focal features resembling traditional serrated adenomas, including ectopic immunohistochemistry in both esophageal adenocarcinoma (EAC) and squamous cell crypt foci, luminal serration, and cytoplasmic eosinophilia. The biologic significance and carcinoma (ESCC). molecular findings associated with this histologic variant of TVA are largely unknown. Design: TMA of 101 EAC and 27 ESCC were immunohistochemically stained for PD- The goal of this study was to investigate the frequency of KRAS and BRAF mutations L1. Expression of PD-L1 was scored for positive, negative and percentage (0-100%) in TVA with serrated features (sTVA) in comparison to a control group of TVA. for positive cells. The data were analyzed byPearson Correlation. Design: 27 consecutive sTVA and a control group of 27 TVA matched for highest Results: Of 101 AC cases, 12 (12%) were positive for PD-L1 immunostain. Of 27 SCC degree of concurrent dysplasia/carcinoma were evaluated. Specimens were analyzed cases, 6 (22%) were positive for PD-L1 immunostain. The PD-L1 expression in EAC for mutations in KRAS codon 12/13 and BRAF codon V600E; other variants in KRAS were significantly correlated with female, but not correlated with other clinicopathologic and BRAF were not evaluated in this study. Somatic variants in KRAS and BRAF were features including age, differentiation, lymph nodes, survival and staging. The mean identified by dideoxy sequencing (assay limit of detection 15%). and median of the percentage of PD-L1 positive tumor cells is 43% and 35% in EAC Results: The mean age of the sTVA group was 68.9 (M:F 1.5:1) and mean age for and is 21% and 15% in ESCC. The PD-L1 expression is not significantly associated the TVA group was 63.0 (M:F 1:1.1). All 27 TVA were wild type for BRAF mutation. with proliferation index Ki67, MCM4 and MCM7. One sTVA (3.7%) was positive for the BRAF V600E mutation. KRAS analysis was Conclusions: PDL-1 expression is relative low in EAC (12%) and ESCC (22%). PD-L1 completed on 22 TVA and 24 sTVA. sTVA were significantly more likely to harbor expression is significantly associated with female. KRAS mutations (66.7% vs. 18.2%, p=0.001). A summary of the KRAS mutations is shown in Table 1. When cases in which KRAS testing was not completed were 624 Prevalence of Immunohistochemically Demonstrable excluded, there was still no significant difference in the distribution for the highest Helicobacter Pylori in Biopsies without Histologic Evidence of Gastritis grade of concurrent neoplasia in the sTVA and TVA groups (p=0.67). Andres Acosta, Michael R Pins. University of Illinois at Chicago, Chicago, IL; Chicago Table 1: Summary of KRAS mutations in TVA and sTVA Medical School, Chicago, IL; Advocate Lutheran General Hospital, Park Ridge, IL. Background: Helicobacter pylori is a major cause of gastritis, with virtually all infected KRAS 12/13 Genotype TVA sTVA patients demonstrating moderate to severe acute and/or chronic inflammation. In fact, G12D 0 (0%) 4 (16.7%) the presence of the bacteria in otherwise normal gastric biopsies is believed to be G12R 1 (4.5%) 0 (0%) rare. Since we perform reflexive immunohistochemistry (IHC) on all gastric biopsies G12S 0 (0%) 1 (4%) with a requisition request to rule out H. pylori, we decided to study the prevalence G12V 1 (4.5%) 5 (21%) of immunohistochemically demonstrable H. pylori in the absence of inflammation (HPy+/Inf-). G13C 1 (4.5%) 1 (4%) Design: We reviewed gastric biopsies with reflexive H. pylori IHC performed in our G13D 1 (4.5%) 5 (21%) institution between 2007 and 2015. HPy+/Inf- biopsies were selected on the basis WT 18 (82%) 8 (33.3%) of the presence of antral mucosa, undetectable or minimal nonspecific inflammation Total: 22 24 and a positive IHC result. All IHCs were performed in the same laboratory under the Legend: TVA=tubulovillous adenoma; sTVA=TVA with serrated features; WT=wild type same protocol. Results: A total of 15,460 gastric biopsies with IHC for H. pylori were evaluated and Conclusions: We confirm results of few prior studies showing more frequent KRAS six HPy+/Inf- cases were initially identified. Of these, two were later demonstrated to mutation in sTVA versus TVA. However, we addressed the shortcoming of prior studies represent H. heilmannii by IHC (2/6 = 33%), making the prevalence of true HPy+/Inf- by controlling for degree of associated dysplasia/carcinoma in our design. KRAS cases 0.0003% (3/10,000 biopsies). All HPy+/Inf- cases were women, with a median mutation is a molecular correlate of the mixed histology of sTVA and may explain the age of 31 yrs (range 4-66 yrs). Of these, one had a history of previously treated H. literature’s tenuous data suggesting a higher risk of advanced outcomes in these polyps. pylori gastritis 4 years prior to the current biopsy. The youngest patient had type 2 Gm1 gangliosidosis with functional immunosuppression, and the remainder two patients did not have significant comorbidities. 622 Age Less Than Forty Is Predictive of Mismatch Protein Loss Conclusions: The prevalence of H. pylori in the absence of inflammation is extremely in Colorectal Tubulovillous Adenomas Sohaib Abu-Farsakh, Danielle Marino, Arthur DeCross, Qi Yang, Loralee McMahon, low (0.0003%), making inflammation a good surrogate for the presence of the bacteria, Jennifer J Findeis-Hosey. University of Rochester Medical Center, Rochester, NY. and an effective trigger for IHC studies when the organism is not readily identifiable Background: Lynch Syndrome (LS) is a genetic syndrome driven by germline mutations on H&E slides. Reflexive IHC upon a request to rule out H. pylori may be justified in in mismatch repair (MMR) protein complexes which result in an increased risk of some institutions for other reasons, such as improved turnaround time. Additionally, numerous neoplasms. Mutations are most frequently encountered in the MLH1, MSH2, IHC might also be considered in biopsies without significant inflammation when there MSH6, or PMS2 genes. Immunohistochemical (IHC) testing using antibodies against the is a history of treated H. pylori gastritis or immunosuppression. Also, in our experience, MMR proteins has been well documented for LS screening in CRC specimens; however, 33% of HPy+/Inf- cases actually represented H. heilmannii infection, thus justifying few studies have examined the use of MMR IHC screening in the general population the immunohistochemical confirmation of this organism in the context of a suggestive before the development of frank malignancy. Here we aim to explore the possibility bacterial morphology. Our data suggest that neither H. pylori “colonization” nor Hpy+/ of LS screening in patients <50 years old who have adenomas with villous features. Inf- purely as a result of the vagaries of random sampling (“sampling error”) occur. Design: Our surgical pathology archives were searched for cases of colorectal adenomas with villous features from 1/1/1997-5/31/2016 in patients < 50 years old. Patients 625 Molecular Lymph Node Staging in Rectal Carcinomas: Can It with a known history of CRC, LS, or familial adenomatous polyposis were excluded. Be Performed? Slides were reviewed and those that did not meet strict criteria for villous morphology Iban Aldecoa, Carla Montironi, Natalia Rakislova, Dulce Momblan, Josep Antoni were excluded. Sixty-nine cases were identified in patients < 45 years old and were Bombi, Francesc Balaguer, Antoni Castells, Antonio Lacy, Miriam Cuatrecasas. Hospital compared to a cohort of 27 cases of patients 45-50 years old recieved between 1/1/2013 Clinic - University of Barcelona, Barcelona, Spain. and 7/31/2015. All 96 cases underwent IHC testing with antibodies against MSH6 and Background: Pathologic hematoxylin and eosin (H&E) lymph node (LN) staging in PMS2. Cases with abnormal staining for either of these proteins underwent additional colorectal carcinomas (CRC) may not provide robust prognostic data, as up to 20% of IHC testing with antibodies for MLH1 and MSH2. Abnormal staining was defined as stage II CRC patients recur from disease within 5 years of intended curative surgery. less than 10% of adenomatous cells exhibiting positive nuclear staining. Recent studies have addressed that molecular staging in colon carcinomas using CK19 Results: Abnormal MMR IHC staining was identified in four out of 31 cases (13%) in mRNA can correlate with classical high risk factors, and there is increasing evidence patients less than 40 years old and in one out of 38 cases (3%) in those 40-45 years old. that it can be used on a daily basis. Nevertheless, there is lack of data regarding the use None of the 27 cases from those 45-50 years demonstrated loss in MMR staining. Of of this technique in rectal carcinomas. the five cases that showed MMR abnormalities, two showed isolated loss of MSH6, one 158A ANNUAL MEETING ABSTRACTS Design: Tumor burden LN detection was performed with the reverse transcription loop- 628 PD-L1 Expression in IBD-Associated Colorectal Cancer and Its mediated isothermal amplification for CK19 mRNA. A total of 493 LN were harvested Relationship to MSI Status, the PI3K Pathway, and HLA-DR Expression from 29 rectal resections without neoadjuvant treatment. In each case, several LN were Lindsay Alpert, Lindsay Yassan, Christopher Weber, Shu-Yuan Xiao, John Hart, Thomas pooled together into PCR tubes for molecular analysis. Krausz, Jeremy Segal, Namrata Setia. University of Chicago, Chicago, IL. Results: The median age of the patients was 68 years, with a male:female ratio of 1.4:1. Background: Programmed death-ligand 1 (PD-L1) expression is rare in colorectal The pTN stages were: 8 pT1, 9 pT2, 8 pT3 and 4 pT4; 23 pN0, 3 pN1a, 2 pN1b and 1 cancers (CRCs), but a subset of tumors with microsatellite instability (MSI), medullary pN2a. A median of 15 LN were dissected per specimen. Using pooling method for LN morphology, and/or increased tumor-infiltrating lymphocytes are known to more analysis, a median of 2 molecular assays were performed per case. Twelve out of 29 frequently express this immunoregulatory molecule. Given the immune-activated cases contained tumoral CK19 mRNA in the lymph nodes, with a median 6300 copies/ background in which inflammatory bowel disease-associated CRCs (IBD-CRCs) arise, µL (IQR 470-30,675). Molecular positivity was correlated to some classical high risk the potential relationship between these tumors and PD-L1 expression is intriguing. factors such as tumor budding, neural invasion and vascular invasion (all p<0.05). A Since the PI3K pathway is a downstream effector of PD-1-activated T cells and genes tendency was observed between CK19 mRNA LN positivity and tumor grade. in this pathway (PTEN, PIK3CA) are frequently mutated in MSI tumors, the mutational Conclusions: Molecular LN staging in rectal carcinoma correlates with some classical status of such genes in IBD-CRCs is also of interest. Additionally, aberrant expression high risk factors and can become more accurate than conventional H&E staging. It is a of HLA-DR was recently identified as a marker of response to anti-PD-L1 therapy in feasible method in daily practice and requires few molecular determinations per case. melanoma. Design: IBD-CRCs resected between 1/2000-7/2015 were identified from the pathology archives. IHC for mismatch repair (MMR) proteins, PD-L1, and HLA-DR 626 Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal was performed on all cases with tumor-containing blocks available. PD-L1 and HLA- Dystrophy (APECED) Associated Gastritis - A Variable Phenotype DR expression in tumor cells were scored according to previously described criteria. Michael Allgaeuer, Elise MN Ferré, Theo Heller, Michail Lionakis, Martha M Quezado. PIK3CA and PTEN mutational status was assessed using a targeted next-generation NCI, NIH, Bethesda, MD; NIDDK, NIH, Bethesda, MD; NIAID, NIH, Bethesda, MD. sequencing panel aimed at 50 cancer-related genes. Background: APECED is a rare condition caused by a mutation in the autoimmune Results: Sixty-two patients with a total of 72 tumors were identified. Five of 58 regulator (AIRE) gene. It manifests with chronic mucocutaneous candidiasis and cases tested (8.6%) were positive for PD-L1, while 32 of 56 cases tested (57.1%) multisystem autoimmunity most commonly leading to hypoparathyroidism and adrenal were positive for HLA-DR. None of the PD-L1-positive cases had a mucinous or insufficiency. Patients frequently develop hepatitis, gastritis, intestinal dysfunction, medullary morphology. PD-L1 positivity was not significantly associated with any and vitamin B12 deficiency. So far the histopathological features of gastritis remain other clinicopathologic characteristics. All 5 PD-L1-positive cases expressed HLA-DR. poorly defined. PIK3CA and/or PTEN mutations were detected in 11/56 tumors tested (19.6%). Loss Design: Available gastric biopsies from 24 patients with a confirmed diagnosis of of ≥1 MMR protein was seen in 3/67 tumors tested (4.5%), all of which also exhibited APECED (biallelic AIRE mutation (21/24; 87.5%) or clinical criteria (3/24; 12.5%)) PIK3CA and/or PTEN mutations. There was no significant association between PD-L1 enrolled in a natural history study were systematically assessed for the presence of positivity and PIK3CA/PTEN mutations or MSI status (p=0.16 and p=0.24, respectively). inflammation, eosinophilic infiltrates, intestinal metaplasia, dysplasia, carcinoma, Conclusions: PD-L1 positivity in IBD-CRCs is rare, but the frequency is similar to that neuroendocrine hyperplasia and H. Pylori organisms. reported in non-IBD-CRCs. Expression of PD-L1 is not associated with MSI status or Results: Sixty-eight gastric biopsies were reviewed by an experienced gastrointestinal PI3K pathway mutations in these tumors, so PD-L1 immunotherapy trials for select pathologist (M.M.Q.) and pathologist-in-training (M.A.). A median of 2 biopsies was microsatellite stable IBD-CRCs should be considered. The findings also support the obtained per patient (range 1-14) in a median of 1 upper endoscopy (1-13). Mean age presence of alternate mechanisms of PD-L1 expression, such as IFN-gamma induced at first procedure resulting in a diagnosis of significant pathology was 22.7 years (3-55) upregulation. Finally, IBD-CRCs that are positive for PD-L1 also express HLA-DR, with 16 (67%) female and 8 (33%) male patients. Inflammation was present in 76.5% which may be an indicator of response to therapy. of biopsies examined (52/68). Inactive chronic gastritis was present in 40 samples and was mild in 33 (33/68, 48.5%), moderate in 6 (6/68, 8.8%), and severe in 1 (1/68, 1.5%). Active chronic gastritis was seen in 8 samples (8/68, 11.8%). Autoimmune atrophic 629 Targeted Mutational Analysis in IBD-Associated Colorectal gastritis (AIG) was confirmed in 4 samples (4/68, 5.9%) of two patients with one sample Cancer displaying linear neuroendocrine cell hyperplasia. All biopsies were negative for H. Lindsay Alpert, Lindsay Yassan, Sabah Kadri, Ibro Mujacic, Nifang Niu, David Montez, pylori. Eosinophils were commonly seen but increased (>15/1HPF) in 1 sample only Filippo D Galbo, Michelle N Wurst, Chao J Zhen, Christopher Weber, Shu-Yuan Xiao, (1/68, 1.5%). Metaplastic changes were mostly absent (59/68, 86.8%). The remaining John Hart, Jeremy Segal, Namrata Setia. University of Chicago, Chicago, IL. biopsies showed complete intestinal metaplasia, either focal (6/68, 8.8%) or prominent Background: Patients with inflammatory bowel disease (IBD) are at increased risk of (3/68, 4.4%). Dysplasia was not identified in the large majority of cases (67/68, developing colorectal carcinoma (CRC). Molecular distinctions between IBD-associated 98.5%). One biopsy was positive for intramucosal signet ring cell adenocarcinoma in CRCs (IBD-CRCs) and non-IBD-CRCs have been noted, including a decreased a background of AIG. Biopsies of that patient 28 months prior showed mild chronic likelihood for IBD-CRCs to exhibit microsatellite instability (MSI). Recently, a study inactive gastritis with focal complete intestinal metaplasia. comparing mutations in cancer-related genes between IBD- and non-IBD-CRCs revealed Conclusions: Chronic gastritis with and without intestinal metaplasia is a common further genomic differences (R Yaeger Gastroenterology, 2016). In the current study finding in patients with APECED and displays various phenotypes including we investigated the mutational profiles of our institution’s IBD-CRCs and compared autoimmune atrophic gastritis. The occurrence of adenocarcinoma appears to be a rare them to published TCGA data. phenomenon, but close follow-up with multiple biopsies may be warranted. Design: IBD-CRCs resected between 2000 and 2015 were identified from the pathology archives. All cases with sufficient FFPE material available underwent molecular testing via a 50-gene hot-spot solid tumor panel utilizing the Ion Ampliseq Cancer Hotspot 627 Lack of Prognostic Significance of HER2 Expression Profile Panel v2 primer set (Thermo Fisher Scientific) for amplification of 207 hotspot targeted in Colorectal Carcinoma amplicons in a single pool. Data was analyzed using a custom-developed in-house Jaudah A Al-Maghrabi, Abdelbaset Buhmeida, Mourad Assidi, Basim J Al-Maghrabi, clinical pipeline, and all variants were annotated using Alamut Batch 1.4.4 software Ashraf Dallol, Adeel Chaudhary, Adel Abuzenadah, Mahmoud S Al-Ahwal, Mohammed (http://www.interactive-biosoftware.com/). H Al-Qahtani. Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia; Results: We identified 72 IBD-CRCs occurring in 62 patients; molecular testing was King Abdulaziz University, Jeddah, Saudi Arabia. successful in 56 cases. The mean duration of IBD at cancer diagnosis was 20 years (SD Background: Traditionally, the utilization of multimodal treatment approach for 11 years) and did not differ significantly according to the type of IBD present (p=0.09). colorectal carcinoma (CRC) has been directed by the TNM staging system. However, The frequency of mutations occurring in >5% of all IBD-CRCs (including 3 cases of the conventional staging system, regrettably, is unable to predict the outcome of patients indeterminate colitis) are listed in the following table: within the same stage. Therefore, finding additional molecular markers that could help in pinpointing the survival outcome and/or treatment response of a group of patients Mutated UC, % CD, % All IBD, % TCGA, % p-value p-value within the same stage will be very helpful towards better management and personalized Gene (n=37) (n=16) (n=56) (n=224) treatment. The prognostic significance of HER2 gene in CRC is not clear and remains TP53 67.6 68.8 0.92 69.6 54.0 0.03 controversial. The objective of this study is to evaluate the association between HER2 KRAS 16.2 31.1 0.27 19.6 42.0 <0.01 amplification/over-expression profile and survival outcome of Saudi CRC patients. PIK3CA 16.2 25.0 0.70 17.9 20.1 0.85 Design: A tissue microarray (TMA) was constructed to contain a total of 243 CRC Formalin Fixed Paraffin Embedded (FFPE) samples of consent patients and stained APC 5.4 31.3 0.02 12.5 75.0 <0.01 by immunohistochemistry (IHC) and bright-field dual in situ hybridization (BDISH) IDH1 5.4 12.5 0.58 7.1 1.3 0.03 methods. The expression patterns of HER2 protein status was correlated to HER2 gene SMAD4 10.8 0.0 0.30 7.1 11.6 0.33 amplification status and assessed for its prognostic value. FBXW7 8.1 0.0 0.55 8.9 16.5 0.16 Results: The expression profile of 99% samples showed cyotplasmic expression patterns of different categories, while, only 1% showed strong (+3) membranous expression There was a trend towards increased PI3K pathway mutations in older patients pattern of HER2 protein and those later samples showed a corresponding amplification (OR=1.07, p=0.055). of HER2 gene status (>2). However, the cytoplasmic HER2 protein status did not show Conclusions: Significant differences exist in the mutational landscape of IBD-associated any significant correlation with different clinico-pathological features and survival and non-IBD-associated CRCs. There is a higher frequency of TP53 and IDH1 mutations outcomes except with age (p<0.04) and tumor size (p<0.03). and a lower frequency of APC and KRAS mutations in IBD-CRCs. The mutational Conclusions: The study revealed that there was no correlation between both profiles of CRCs in CD and UC also differ; CD CRCs are more likely to exhibit APC membranous and/or cytoplasmatic HER2 expression and patient’s survival outcome mutations, while SMAD4 and FBXW7 mutations may be specific to UC CRCs. either disease-free and/or disease-specific survival among CRC patients. ANNUAL MEETING ABSTRACTS 159A 630 Equivocal CMV Staining by IHC: Frequency and Clinical Design: We evaluated 22 hepatocellular carcinomas (21 whole sections and 1 core Signifi cance in a tissue microarray [TMA]), and neoplastic (12) and non-neoplastic tissue (9) in Manju Ambelil, David Saulino, Atilla Ertan, Andrew W Dupont, Sushovan Guha, a TMA with 2 cores each (as shown in Table 1). We performed RISH for albumin Mamoun Younes. University of Texas Health Science Center at Houston McGovern using the RNAscope detection kit (Leica Biosystems, Buffalo Grove, IL) with the Medical School, Houston, TX. Bond III autostainer, using probe Hs-ALB-01 (Advanced Cell Diagnostics, Newark, Background: Recent studies examining immunohistochemical (IHC) staining of CA). A negative probe, Dap B, and a positive probe for RNA (PP1B) were also colorectal biopsies for CMV reported that some cases showed rare small positive included. Characteristic dot like cytoplasmic reactivity was considered positive. A nuclei that were called equivocal for CMV. The aim of this study was to determine the semiquantitative method of scoring was used: 0=no staining at all; 1= <5% tumor cells; extent of equivocal IHC staining for CMV, and whether it is of clinical signifi cance. 2 = 5-50% tumor cells and 3= > 50% tumor cells. Design: During a two-year period, 2014 and 2015, two hundred twenty-one cases of Results: Albumin RISH was diffusely positive (3+) in 22 of 22 HCCs (fi gure 1) and colon and rectal biopsies were stained for CMV by IHC. Slides were reviewed and 1 neonatal liver. staining results were recorded as negative when there was completely negative nuclear staining, “unequivocal” when at least one large “megalic” nucleus positively stained, and “equivocal” with only small positively stained nuclei without any positive large (megalic) nuclei. Clinical data were obtained from the medical records. Results: A total of 83 (38%) of the 221 cases showed nuclear staining in at least one cell. Fifty-two cases (24 % of all tested, 63 % of all positive case) showed equivocal staining. Of these equivocal cases, 4 had completely normal histology, and 9 showed mild nonspecific changes. In the pathology reports, unequivocal staining was reported to the clinicians as “rare” or “occasional” small nuclei positive for CMV by immunoperoxidase staining. Twenty-nine of the patients with equivocal biopsies were treated with antiviral drugs or discontinuation of immunosuppressive drug and of these 24 (83%) had signifi cant improvement or complete resolutions of the disease/diarrhea. By contrast, only 5 of 14 (36%) patients with equivocal staining who did not receive specifi c treatment improved (p=0.002). Documentation on treatment and/or follow-up was not available for 9 patients with equivocal staining. One of the fi ve patients with equivocal staining who did not respond to antiviral treatment had a fl are up of IBD which was the reason for worsening of symptoms. Table 1. Albumin RISH Conclusions: In summary, more patients tested for CMV by IHC show occasional Tissue Type Albumin RISH Stain Result positive small nuclei than classic megalic nuclei, including transplant recipients with Tonsil - normal or minimal nonspecifi c histology and chronic diarrhea. The majority of these patients respond well to specifi c antiviral treatment. Therefore 1) all colorectal biopsies Normal Breast - from immunosuppressed patients, even with normal histology, should be tested for Placenta - CMV by IHC and 2) rare small positive nuclei should be reported to the clinicians as Prostate - positive for CMV. Colon - Skin - 631 Colonic Carcinomas with Sporadic Loss of Mismatch Repair Spleen - Proteins Are Associated with Loss of HLA Class I Kshitij S Arora, Theodoros Michelakos, Lei Cai, David T Ting, Cristina Ferrone, Salivary gland - Soldano Ferrone, Vikram Deshpande. massachusetts General Hospital, Boston, MA. Neonatal Liver + Background: The programmed death 1 (PD-1) pathway represses cytotoxic immune Breast Carcinoma - responses and protects tumors from the intratumoral T-cell infi ltrate. Gastrointestinal Renal Cell Carcinoma - neoplasms with defective mismatch-repair (MMR) status show dramatic and durable Medullary Thyroid Carcinoma - clinical benefi t of immune checkpoint blockade with PD-1 antibodies, however, only half the MSI (microsatellite instability) positive colon carcinomas respond. Herein, Melanoma - we explore three escape mechanisms that may predict resistance to PD1 therapy: 1) Pancreatic NET - absence of PDL1 expression, 2) absence of PD1 expression, 3) loss of tumor HLA Ovarian Carcinoma - class 1 proteins. We also validate the immunohistochemical (IHC) assay using a branch Mesothelioma - chain ISH assay for PD-L1. Leydig Cell Tumor - Design: 96consecutive colonic adenocarcinomas without evidence of Lynch syndrome were evaluated to determine MSI status, PD-L1 reactivity, and HLA Class I antigen Thymoma - expression. MSI status was evaluated on an IHC platform using antibodies against HCC + MLH1, PMS2, MSH2 and MSH6. IHC for PDL1 (clone E1L3N ) and Class I HLA (clone Papillary Thyroid Carcinoma - HC10) was performed. In situ hybridization (ISH) for PD-L1 and PD1 (Affymetrix, Colon Carcinoma - CA) was performed. The results were validated using TCGA colon cancer dataset. Results: Neoplastic cells express Class I HLA at the advancing edge of the tumor. All the other neoplastic (12, 100%) and non-neoplastic (9, 100%) were negative. 10 Tumors with MSI loss were more likely to show loss of HLA class I (MSI loss 29% of 22 HCCs were poorly differentiated carcinomas, all of which were positive for (7/24), MSI intact 7% (5/72) (p=.0.004). PDL1 IHC was positive in 41% of cases and Albumin RISH. detected in either macrophages (31%) or tumor cells (9%). PD-L1 ISH correlated Conclusions: In our cohort, Albumin RISH showed a sensitivity of 100% and specifi city strongly with PD-L1 IHC (Pearson correlation 0.78); ISH signal was noted in either of 100%. Albumin RISH appears to be a useful marker, also in poorly differentiated macrophages or tumor cells. Tumors with MMR protein loss were more often positive for HCCs, when other hepatocellular markers may be negative. PD-L1, in both macrophages and tumor cells (p=0.02); this correlation was validated on the TCGA cohort (p=0.0001). 21% of tumors with loss of MMR proteins expressed PD- 633 Peritumoral Lymphoid Cuff in Gastrointestinal Schwannomas L1 in tumor cells compared to 5% in the MSI intact cohort. PD1 positive lymphocytes Is Signifi cantly Correlated with Regional Lymph Node Enlargement: A (> 10/HPF) correlated with positive PDL1 staining in neoplastic cells (p=0.03), but Study of 118 Consecutive Cases from a Single Institute not with PDL1 staining in macrophages (p=0.18). All tumors with PD-L1 reactivity in Hyunsik Bae, Ha Young Park, Jinah Chu, Michael Van Vrancken, Kyoung-Mee Kim. neoplastic cells were also positive for PD1 lymphocytes. Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Conclusions: The high rate of loss of HLA class 1 in tumors with sporadic loss of Republic of Korea; Tulane University School of Medicine, New Orleans, LA. MMR proteins represents a common escape mechanism in this class of tumors and Background: Primary schwannomas of the gastrointestinal (GI) tract are uncommon may predict resistance to immunotherapy. IHC analysis of PD-L1 and class I HLA may subepithelial lesions that usually follow a benign course, although rare cases of malignant assist in tailoring checkpoint inhibitor therapy in colonic carcinomas. transformation have also been reported. The distinction between schwannomas and gastrointestinal stromal tumors (GIST), another subepithelial GI tract tumor, is an 632 Albumin RNA In Situ Hybridization in Hepatocellular important aspect in the preoperative planning of these lesions. One helpful distinction Carcinomas and Other Neoplastic and Non-Neoplastic Tissue: Can This that has been reported is that regional lymphadenopathy (LAD) is more often associated Be a Clinically Useful Marker? with schwannomas than with GISTs. Vaidehi Avadhani, Momin T Siddiqui, Diane Lawson, Cynthia Cohen. Emory University, Design: The Samsung Medical Center pathology database was queried for all resected Atlanta, GA. gastrointestinal schwannomas from January 1998 to June 2016. A total of 118 cases Background: RNAscope is an RNA in situ hybridization (RISH) technology with were found. a unique signal amplifi cation and background suppression strategy. Albumin is a Results: Locations of the lesions varied and included 85 gastric (72%), 11 colonic well-known sensitive and specifi c marker for hepatocellular carcinoma (HCC) but (9.3%), 7 esophageal (5.9%), 3 pancreatic (2.5%), 1 hepatic (0.8%), and 11 peritoneal immunohistochemical detection has proven to be diffi cult practically. With the current (9.3%). The female to male ratio was 1.7:1, and ages ranged from 25 to 80 (mean 55.5) use of RISH, we evaluated the effi cacy of albumin ISH as a marker of HCC and years. The size of the tumors ranged from 0.2 to 11 cm with a mean of 3.8cm. None compared its use in other neoplastic and normal tissues. of GI schwannomas recurred or showed any evidence of malignant transformation. Histologically, in the majority of cases (75 cases - 63.6%), a peripheral lymphoid cuff 160A ANNUAL MEETING ABSTRACTS was noted around the schwannoma ranging in thickness from 0.5 to 6 mm (mean 2.8 636 RICTOR Overexpression/Amplification in Advanced mm). Regional LAD was assessed through review of prior radiographic and concurrent Solid Tumors; a Correlation Study Utilizing Immunohistochemistry, pathologic findings. Of the 106 cases for which data was available for, 48 cases (45.3%) Fluorescence In Situ Hybridization, and Targeted Sequencing showed regional LAD. The presence of the lymphoid cuff and regional LAD showed Heejin Bang, Soomin Ahn, Jeeyun Lee, Seung Tae Kim, Michael Van Vrancken, Ha significant positive correlation (p=0.002). Young Park, Kyoung-Mee Kim. Samsung Medical Center, Sungkyunkwan University Conclusions: Within the GI tract, schwannomas are a rare entity which need to School of Medicine, Seoul, Korea; Ewha Womans University School of Medicine, be distinguished from GISTs. The presence of regional LAD favors schwannoma. Seoul, Korea; Tulane University School of Medicine, New Orleans, LA; College of Histologically, a peripheral lymphoid cuff is seen in the majority of GI tract Medicine, Inje University, Busan Paik Hospital, Busan, Korea. schwannomas and positively correlates with the presence of regional LAD. However, Background: RICTOR is a key component of the mTOR complex 2 (mTORC2). When in a significant subset (36.4%), no lymphoid cuff is present magnifying the importance activated, this complex promotes cellular proliferation and survival through of correlating preoperative radiologic studies and postoperative pathologic diagnoses the activation of downstream AGC kinase family members. Amplification of RICTOR in the distinction between GI tract schwannomas and GISTs. serves as a promising emerging actionable genomic alteration for which targeted therapy will likely be developed. However, the incidence of RICTOR amplification in advanced solid tumors is an area that has not been fully explored. 634 Prognostic Significance of Tumour Regression Grade at Design: In this study, a multimodal design was used in order to study RICTOR Primary Site and Its Correlation with Clinical and Histological Parameters amplification through the use of immunohistochemistry (IHC; n=416), fluorescence in in Post Chemotherapy Excision Specimens of Oesophagus-Single situ hybridization (FISH; n=51) and deep targeted sequencing (n=51) in a number of Institutional Study solid organ tumors including colorectal (n=193), gastric (n=86), renal cell carcinoma Ganesh Bahirwade, Shubhada Kane, Rajiv Kumar, Swapnil Rane, Anuj Verma, Kumar (n=34) and other solid cancers (n=103). These cases were previously also enrolled for Prabhash, Pramesh Shanmugham. Tata Memorial Hospital, Mumbai, India. NEXT1 and NEXT2 trials. For IHC, cases were considered positive if there was +1, Background: Carcinoma of oesophagus is one of the most lethal malignancies. Surgery +2, or +3 staining. Blush weak to negative staining was considered negative. For FISH, is the main treatment modality. Neoadjuvant chemotherapy helps to reduce the tumour a RICTOR/CEP17 ratio >2.0 was defined to be amplified. For targeted sequencing, an burden and increases survival when followed by surgery. Histological assessment estimated copy number ≥4 was considered amplified. of tumour response-tumour regression grade(TRG), its prognostic significance and Results: RICTOR was overexpressed in 202 cases (48.6%; 1+, 30.3%; 2+, 14.4%, correlation with clinical and histological parameters is not extensively studied in cases 3+, 4.1%) by IHC, and amplified in 29 cases (56.9%) by FISH and 24 cases (47.1%) of carcinoma oesophagus. This study focuses on correlation of TRG with clinical, by targeted sequencing. Overexpression/amplification of RICTOR was found in 111 histological parameters and survival (DFS/OS.) (57.5%) colorectal cancers, 38 (44.2%) gastric cancers, 16 (47.1%) renal cell carcinomas, Design: One hundred forty cases of post NACT excision specimens of oesophagus and 37 (35.9%) other tumors. The IHC results were significantly positively correlated during the year 2014 were retrieved from hospital registry. Follow up details were with FISH (p<0.0001; r=0.66), but no significant correlation was seen between IHC obtained from electronic medical record. Histology sections were reviewed, TRG and targeted sequencing (p=0.49). was assigned in each case using Mandard grading system. Clinical and histological Conclusions: In conclusion, RICTOR overexpression/amplification is fairly common parameters such as tumour size, site of involvement, histologic type, pTNM stage, in a variety of advanced solid tumors. Additionally, IHC for RICTOR appears to circumferential resection margin(CRM), tumour grade and survival were correlated be a reliable surrogate marker for amplification, which may very well have future with TRG. Statistical analysis was performed with Kaplan Meier test, log- rank test therapeutic implications. and Chi square test. Results: Distribution of TRG 1-5 was as follows: TRG 1-26.4%, 2-10%, 3-10%, 4-22.5% and 5-31.5%, TRG was significantly correlated with pre- chemotherapy size 637 Low Grade Appendiceal Mucinous Neoplasms with Neoplastic (largest dimension) of the tumour, site of involvement, histologic type, pTstage, pN Epithelium Confined to the Appendix: 45 Cases with Clinical Follow-Up stage and CRM status. TRG was significantly correlated with DFS but not with OS. Brad D Barrows, Deepti Dhall. Cedars Sinai Medical Center, Los Angeles, CA. Conclusions: This study confirms the importance of grading tumor regression in the Background: Appendiceal mucinous neoplasms continue to be a challenge for survival of patients with esophageal carcinoma with neoadjuvant chemotherapy. It pathologic classification and clinical management. The World Health Organization also suggests that TRG should be evaluated in post NACT oesophagectomy specimen. (WHO) divides these tumors into three categories: adenoma (low grade dysplastic mucinous epithelium with intact muscularis mucosa), low grade appendiceal mucinous neoplasm (LAMN) (mucin and/or dysplastic epithelium beyond the muscularis mucosa, 635 Unique Differential Expression of PD-L1 in Anal Squamous including extra-appendiceal low grade neoplastic epithelium and/or mucin), and Cell Dysplasia and Invasive Carcinoma mucinous adenocarcinoma (infiltrative invasion). The anxiety concerning a diagnosis Andrew Bandy, Xiaoming You, Haonan Li, Jie Liao, Sambasiva Rao, Guang-Yu Yang. of LAMN in routine clinical practice can be at least partly attributed to the limited Northwestern University, Chicago, IL. number of outcome studies to guide management. This single institutional study will Background: Escape from immune surveillance is crucial in tumor development for focus on the clinical behavior of 2 subgroups of LAMN: mucin pools and neoplastic avoiding death via upregulation of programmed death ligand 1 (PD-L1) on their cell epithelium confined by appendiceal serosa and cases with acellular mucin alone beyond surface and becoming functionally anergic to the immune system. Recently much the appendiceal serosa. research has focused on the expression level of PD-L1 on tumor cells and targeting Design: 104 appendiceal mucinous neoplasms (entirely submitted for histologic PD-L1 with immunotherapy which overcomes this stealth mechanism and boosts examination) were retrieved from the Pathology database (1995 - 2016). 45 cases the immune response. With limited data regarding PD-L1 status in patients with anal met our inclusion criteria (extended follow-up defined as > 6 months and absence of squamous cell carcinoma (SCC), it is worth determining whether PD-L1 is expressed neoplastic epithelium outside the appendiceal serosa). in HPV-associated anal SCC since HPV-positive head and neck SCC have higher PD- Results: Two subgroups of LAMN were identified: 36 cases with mucin and neoplastic L1 expression and benefit from anti PD-L1 drugs, and whether there is a difference in epithelium confined by appendiceal serosa and 9 cases with extra-appendiceal acellular PD-L1 expression in HPV-associated dysplasia compared to SCC. mucin. All were managed by either appendectomy (n=34; 4 with partial cecectomy) Design: A total of 42 patients with either in situ and/or invasive anal SCC from 37 or partial colectomy (n=11). No tumor recurrence was noted in either group at a biopsies and 5 resections were collected. Immunohistochemistry for p53, p16 and PD- mean follow-up of 54 months (median 50 months, range 7-146). Interestingly, all 4 L1 was performed for all cases with proper positive and negative controls. Positive appendectomies with positive proximal margin had no residual lesion in subsequent staining was evaluated based on staining intensity in either the membrane, cytoplasm hemicolectomy specimens. However, one patient was noted to have a single focus of or nuclei of tumor cells (negative, weak, moderate and strong) and the proportion of acellular mucin removed as an omental nodule at the time of colectomy, and this patient overall tumor that stained (% positive cells). has been disease free through 74 months of follow-up. Results: In this cohort, All 42 cases (100%) displayed HPV-associated diffuse or Conclusions: Our study adds to the literature supporting an excellent prognosis with intense cytoplasmic/nuclear positive p16 staining in the high grade dysplasia/in situ negligible risk of recurrence in cases of LAMN confined within the appendiceal serosa. and invasive SCC, and all cases exhibited scattered p53 positive cells (wild-type p53 These tumors may be best treated (or even cured) by appendectomy alone. Right protein). For PD-L1, 17/31 (55%) cases displayed at least moderate staining in tumor hemicolectomy may not be necessary even in cases noted to have low grade mucinous cells in the invasive component of anal SCC (Fig A), with a similar staining profile seen dysplasia at margin. Regular follow-up with colonoscopy including observation of the in 7/30 (23%) cases of high-grade dysplasia (Fig B). All background normal squamous appendix resection site may be a more efficient method of recurrent disease monitoring. mucosa in 14 cases was negative for expression of PD-L1 (Fig C). 638 Indoleamine 2,3-Dioxygenase 1 (IDO1) Expression in Biliary Tract Cancers Prashant Bavi, David Hedley, Jennifer J Knox, Stefano Serra. University Health Network, University of Toronto, Toronto, ON, Canada; Clinical Oncology, University Health Network, University of Toronto, Toronto, ON, Canada. Background: Indoleamine 2,3-dioxygenase 1 (IDO1) is one of the key rate limiting enzymes involved in tryptophan metabolism through the kynurenine pathway. IDO1 Conclusions: Our study demonstrated that PD-L1 is upregulated in anal HPV-associated has been shown to exert an immunosuppressive effect in the tumor microenvironment invasive SCC and high-grade dysplasia compared to non-dysplastic squamous mucosa. and prevent exaggerated T cell response. Here, we investigate IDO1 as a potential Additionally, the high frequency of PD-L1 expression in invasive SCC suggests PD-L1 prognostic marker in biliary tract cancerand correlate its expression with clinic- may serve as a potential biomarker to predict progression from in situ SCC to invasive pathological variables. SCC. Our data imply a potential benefit for anal SCC patients with IHC expression of Design: We investigated IDO1 expression by immunohistochemistry in a well- PD-L1 by incorporating immunotherapy into their treatment regimen. characterized tissue microarray cohort of 161 biliary tract cancer patients. Anti- hIDO ANNUAL MEETING ABSTRACTS 161A mAb (cl4.16H1), a purified 4.16H1 anti-IDO1 antibody, Ludwig Institute for Cancer Research Ltd., was used. IDO1 expression was grouped into present and absent based on cytoplasmic and/or nuclear expression observed in the tumor and the stromal cells. IDO1 expression was correlated with tumor pathological features including TNM staging as well as clinical outcomes such as overall survival. Results: IDO1 expression in the tumor was observed in 34.7 % (56/161) of stage I-IV biliary tract cancers. IDO1 expression correlated with tumor size(p= 0.00251; <3 cm), perineural invasion (p=0.0173), lack of tumor vein invasion (p=0.0191), and site (p=0.0099; 56 % of bile duct cancers). IDO1 expression was not associated with age, Stage, histology and lymph node involvement. No differences in overall survival (p=0.2287) or recurrence free survival were observed in tumors with and without IDO1 expression. However, biliary tract cancers from hilar site with IDO1 expression showed a poor overall survival(p=0.0317) as compared to those with no IDO1 expression. Conclusions: IDO1 expression was observed in a significant subset of biliary tract carcinomas. Our results highlight subgroups of biliary tract cancer patients from hilar site with IDO1 expression are more aggressive, and further studies in a larger cohort could act as an adjunct to decide on IDO1 adjuvant treatment strategies in these patients. There is no association among Nestin expression , tumor grade, lymph node status, angiolymphatic invasion and perineural invasion. Conclusions: Nestin is considered as a stem cell marker which showed prognostic 639 Spectrum of Histopathological Changes Induced by PD-1/PD-L1 value in animal and cell lines studies. Our study showed that Nestin expression can be Blockade in GI Biopsies: A Preliminary Study detected in a subset of PDACs, and not associated with common prognostic markers. Prashant Bavi, Stefano Serra, Marcus Butler, Runjan Chetty. University Health Network, Toronto, ON, Canada; Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada. 641 TTF-1 Expression Is Upregulated in the Corpus in Autoimmune Background: Immunotherapy targeting programmed cell death protein 1 and its Atrophic Gastritis ligand (PD-1/PD-L1) have dramatically improved outcome in multiple tumors. There Ava Bhattarai, Andrew M Bellizzi. University of Iowa, Iowa City, IA. is a paucity of data on the histopathologic features of PD-1/PD-L1 inhibitors (PDIs) Background: We routinely perform a panel of site of origin immunohistochemistry induced immune related adverse events (irAEs) in the GI tract. (IHC), including occasionally TTF-1, in metastatic neuroendocrine tumors (NETs) Design: We identified 144 patients on combination clinical trials with PDI (2011-2016) of occult origin. Upon accidentally staining a gastric NET arising in autoimmune from the Tumor Immunotherapy Program database at The Princess Margaret Cancer metaplastic atrophic gastritis (AMAG), we discovered strong TTF-1 expression in Centre. Of these 18 patients underwent GI endoscopy and biopsy for symptoms clinically the background mucosa. As AMAG is characterized by intestinal and pancreatic attributed to irAEs. Patient electronic medical records were reviewed for type of acinar metaplasia, we speculated that at least a portion of what is referred to as pyloric primary tumor, start and stop dates of therapy, types of therapy, endoscopy findings and metaplasia in this setting may in fact be bronchopulmonary metaplasia. history of autoimmune disorders. Histopathologic changes such as architecture, surface Design: TTF-1 IHC was performed in 33 AMAG (22W:11M; mean age 59; 48 corpus, ulceration, cryptitis, crypt abscesses, apoptosis of basal crypt, dilated damaged crypts, 24 antral biopsies), 43 Helicobacter pylori (HP) gastritis (20W:23M; mean age 43; expansion of lamina propria, lymphoplasmacytic infiltrate, granulomas, lymphocytic 50 biopsies), and 19 non-gastritis patients (9 full-thickness sections from sleeve colitis, microscopic colitis were studied. Immune infiltrate was characterized in the gastrectomies, 10 normal corpus biopsies). HP biopsies were assessed for gastritis intraglandular compartment and lamina propria using a IHC panel of CD3, CD8, CD4, topography: corpus-predominant (CP), pangastritis (PG), antral-predominant (AP). FoxP3, CD20 and CD4. We also stained other pyloric metaplasias (20 chronic carditis, 13 chronic ileitis, 22 Results: There were 11 men and 7 women with an age range of 24-74 years. The chronic cholecystitis) and tubal gut adenocarcinomas (18 esophagus, 36 stomach, 23 study cohort consisted of 36 GI biopsies: large intestine (n=24); small intestine (n=5); small intestine, 46 colon). For biopsies, TTF-1 was quantified as mean number of stomach (n=5) and others (n=2; pancreas and esophagus). Colonoscopy findings ranged TTF-1-positve glands/biopsy fragment. Two-sided Fisher’s exact, Mann-Whitney, and from normal to colitis to erythematous friable and ulcerated mucosa. Patients with Kruskal-Wallis tests were used (p<0.05 significant). symptomatic clinical PDI-induced colitis did not show any significant histological Results: TTF-1-positivity was seen in 40/48 (83%) corpus and only 3/24 (13%) antral changes in most of the intestinal biopsies (18 biopsies from 7 patients). However, biopsies from 29/33 (88%) AMAG patients; 14/50 (28%) biopsies from 14/43 (33%) striking changes reflecting a mixture of inflammatory bowel disease, drug induced HP gastritis patients; and 7/9 (78%) sleeve gastrectomy sections and 4/10 (40%) normal toxicity and graft versus host disease changes were noted in only 10 biopsies from 3 corpus biopsies. The mean (median; range) number of TTF-1-positive glands/fragment patients. The mean CD3 (p=0.0019) and CD8 (p=0.0019) counts in the intraglandular was 8.5 (4.5; 0-42) for AMAG corpus, 0.46 (0; 0-5.5) for HP gastritis, and 0.20 (0; compartment were significantly higher in the PDI treated group as compared to the 0-1) for normal corpus biopsies. TTF-1 was not expressed in 20 chronic carditis and control group with IBD. 13 chronic ileitis biopsies or in 123 tubal gut adenocarcinomas; 1/22 (5%) chronic Conclusions: No specific histological features were identified that could distinguish cholecystitis cases was focally positive. On a per patient and per biopsy basis, the PDI induced colitis and irAEs from other colitis. However, presence of multiplicity frequency and extent of TTF-1-positivity was significantly greater in AMAG than HP of histological patterns in the same biopsy and a significant increase in intraglandular gastritis (all p<0.0001). Extent of TTF-1-positivity did not significantly differ between CD3 and CD8 lymphocytes were noted. For correct diagnosis of such type of colitis, HP gastritis and normal (p=1), and HP gastritis topography did not reach statistical awareness of irAEs and treatment history will be the cornerstone of diagnosis significance for frequency (p=0.054) or extent (p=0.23) of positivity. Thresholds of ≥2 and ≥3 TTF-1-positive glands/fragment were 70% sensitive, 91% specific and 58% sensitive, 98% specific for a diagnosis of AMAG (vs. HP gastritis). 640 Prognostic Value of the Nestin Staining in Human Pancreatic Conclusions: TTF-1 is significantly overexpressed in atrophic gastritis, a finding that Ductal Adenocarcinoma is both biologically intriguing and potentially diagnostically useful. Mohadese Behtaj, Wei Xin. University Hospitals Cleveland Medical Center/Case Western Reserve University, Cleveland, OH. Background: Nestin, a class VI intermediate filament protein, detected in neural stem 642 Chromosome 17 Copy Number Instability Is Associated cells during development. The expression of nestin has been detected in various human with Favorable Prognosis in Non-Surgically Treated Gastroesophageal malignancies. Multiple study showed nestin is a stem cell marker of pancreatic ductal Adenocarinoma but May Impair Response to Trastuzumab adenocarcinoma (PDAC) in cell lines. The primary aim of this study is to investigate Jacqueline Birkness, Neal Spada, Sanja Dacic, James D Luketich, Katie S Nason, nestin expression in human PDACs and a possible prognostic marker. Weijing Sun, Jon Davison. Johns Hopkins University, Baltimore, MD; University of Design: 175 cases of PDAC were studied by tissue microarray (TMA), ranging from Pittsburgh, Pittsburgh, PA. 29-85 year old, and F/M: 94/81.Immunostain of Nestin was performed in the hospital Background: Chromosomal instability (CIN), defined as variation in chromosome diagnostic lab; the staining was scored and correlation with clinical findings was copy number, has been shown to result in unstable aneuploidy. In esophageal evaluated. adenocarcinoma, chromosome 17 (Chr17) aneusomy is associated with heterogeneous Results: Among the 175 cases, only 23% (41/175) showed detectable nestin expression. HER2 amplification, a marker of poor prognosis [PMID: 22987085], but the association between Chr 17 CIN (CIN17), Chr17 aneusomy and response to trastuzumab has not been studied. Design: We retrospectively analyzed individual cell Chr17 centromere counts (≥60 cells per tumor) in 348 gastroesophageal adenocarcinomas that were tested for HER2 amplification by FISH. As an estimate of CIN17, we calculated the percentage of cells with centromere counts differing from the mode (modal centromere deviation, MCD) [PMID: 21784954]. We analyzed the association of CIN17 with Chr17 aneusomy, HER2 amplification (HER2/CEP17>2.0), histologic type and clinical outcome. Results: We found 45% (158/348) of tumors were positive for CIN17 (MCD≥30%) and 28% (99/348) positive for extreme CIN17 (MCD>45%). CIN17 positive tumors were more likely to be polysomic and Lauren intestinal type, but there was no association with between CIN17 and HER2 amplification (figure 1A, B, C). In patients who received primary chemotherapy (n=77), there was a 58% reduction in overall mortality associated with extreme CIN17 (HR=0.42, 0.25-0.72, P=0.002) independent of age, stage and addition of trastuzumab. Addition of trastuzumab to chemotherapy showed a Normal ductal, acini and islet do not show detectable nestin staining. 162A ANNUAL MEETING ABSTRACTS trend toward prolonged survival compared to chemotherapy alone only in the subgroup Thus defi ning prognostic biomarkers to more accurately determine each person’s risk of without extreme CIN (P=0.054). In patients treated by surgery, CIN17 was not associated relapse and need for chemotherapy is a priority in colorectal cancer research. Myosin 1e with differences in survival. (MYO1E) a long-tailed, class I myosin, regulates endocytosis, adhesion, migration, and invadosomes in kidney podocytes. Despite MYO1E expression in numerous cancers, its association with tumor progression is poorly understood. Design: MYO1E was examined by IHC in CRC and matched normal adjacent tissue (NAT). A tissue microarray constructed from 119 CRC patients with available formalin fi xed paraffi n embedded tumor and NAT blocks and clinical annotation and included duplicate cores from each tissue block. Semiquantitative MYO1E immunohistochemical H-scoring was conducted by blinded surgical pathologists. Next, the ratio of MYO1E tumor/NAT expression was calculated for each patient with both intact tumor and matched NAT tissue Results: The ratio of MYO1E tumor/NAT expression was negatively associated with stage progression and increased invasiveness of tumors characterized by T-score. Moreover, tumors that had spread to regional lymph nodes had a signifi cantly lower Myo1e expression ratio than tumors localized at the primary site. These data provide clinical evidence that reduced expression of Myo1E, compared to matched NAT, is associated with disease progression. Conclusions: This study identifi es MYO1E as a potential prognostic biomarker in CRC. Further examination of MYO1E expression to predict disease relapse and survival in a large retrospective study of CRC patients is suggested to defi ne its prognostic utility to improve the clinical management of CRC patients. 645 Incidental Gallbladder Carcinoma Associated with Dysplasia and Acute Cholecystitis D E Bosch, M M Yeh, R A Schmidt, P E Swanson, C D Truong. U of Washington, Seattle, WA. Background: Gallbladder carcinoma (GC) is an uncommon malignancy with an Conclusions: CIN can be quantifi ed from routine centromeric FISH data. Extreme overall 5-year survival of less than 5%. Due to overlap of clinical presentation with the CIN17 was a favorable prognostic factor after primary pharmacologic therapy, but more common cholecystitis, it is estimated 50-65% of all GCs are found incidentally. could impair response to trastuzumab. Epithelial dysplasia is identifi ed in ~50% of specimens with invasive carcinoma. Recent expert panel guidelines have recommended histologic examination of the entire gallbladder in cases where initial sampling reveals dysplasia. Acute cholecystitis is 643 ErbB3 Overexpression Predicts Survival in Primary Colorectal frequently associated with GC and may complicate interpretation of epithelial atypia; Cancer however, its relationship to patient outcomes is unknown. Alina Bocicariu, Kevin Yi Mi Ren, Ravi Ramjeesingh, Nazik Hammad, James J Biagi, Design: We searched cholecystectomies with either dysplasia or GC within the last 15 Christopher Nicol, Lois Mulligan, Harriet Feilotter, David Hurlbut, Scott Davey. years at our institution. For cases reporting additional sectioning after initial histologic Queen’s University, Kingston, ON, Canada; Dalhousie University, Halifax, NS, Canada. evaluation, slides were reviewed. Gallbladder imaging reports were reviewed for all Background: ErbB3 is a member of epidermal growth factor receptor (EGFR) gallbladder carcinoma cases, when available. Patient demographic, clinical, and survival family and has dual roles in promoting cell proliferation and preventing apoptosis information was gathered from the medical record and publicly available databases. through activation of PI3K/AKT pathway. ErbB3 as a heterodimerization partner also Results: 89 cases of GC, 34 high grade dysplasia (HGD), and 60 low grade dysplasia promotes tumor invasion and metastasis in many solid tumors. ErbB3 expression and (LGD) were identifi ed. Pre-operative imaging (either ultrasound or CT) only identifi ed its correlation with the clinical outcome in primary colorectal cancer (CRC) have been 52% of mass lesions in GC cases. Distant metastases were identifi ed by post-operative assessed in a limited number of studies with contradictory results. We examined ErbB3 imaging in 44% of cases. Among gallbladder specimens with epithelial dysplasia only expression in a large cohort of primary CRC and assessed its performance as a potential at initial sampling, additional sectioning was performed and reported in 59% of HGD independent prognostic marker. and 55% of LGD. Invasive carcinoma was identifi ed after additional sectioning in 3 of Design: ErbB3 expression was assessed by immunohistochemistry using tissue 20 HGD (15%) and 0 of 28 LGD cases. In multivariate analysis, signifi cant correlations microarrays from 128 cases of primary CRC patients (stage I-IV) treated in our with decreased survival were found for specimens with associated acute cholecystitis institution. Intensity and extent of ErbB3 staining were independently assessed by (HR 6.5, p=0.001), positive liver bed or cystic duct margins (HR 3.4, p=0.008), and 2 pathologists on a scale from 0 to 3. Cytoplasmic (c) and membranous (m) erbB3 distant metastases (HR 2.2, p=0.05). staining scores were calculated as a weighted average from 3 core samples per tumour. Conclusions: A high percentage of GCs are identifi ed incidentally on routine histologic Univariate analysis of average scores and clinicopathological outcome measures from examination of gallbladder specimens, in part due to low sensitivity of pre-operative patient chart review was completed. imaging. Additional sectioning of gallbladder specimens with HGD has a higher yield Results: ErbB3 is overexpressed in CRC compared to normal colonic epithelium (15%) for identifying invasive carcinoma than those with LGD (0%). In our cohort, (n=119; p=0.01). The proportion of positive lymph nodes per case was positively positive margin status and associated acute cholecystitis were signifi cantly associated associated with higher membranous and cytoplasmic erbB3 expression level in tumour with reduced survival. cells (n=125; p<0.01). Both cytoplasmic and membranous ErbB3 overexpression in tumor cells were associated with improved 2-year survival (n=128; p=0.02 and p=0.03, respectively), but were not associated with conventional prognostic factors such as 646 PD-L1 and PD-1 Expression Profile Depending on the tumor stage, lymph node involvement and lymphovascular invasion. Microsatellite Status and the Histological Subtype in Colorectal Conclusions: Our fi ndings show that ErbB3 overexpression in primary CRC is Carcinomas associated with better 2-year survival. Given the divergent results of the role of ErB3 Céline Bossard, Eva Ott, Delphine Dansette, Adrien Ouairy, Anne Jarry, Stéphane expression in primary CRC reported in the literature, standardizing ErbB3 expression Bezieau, Claire Toquet, Jean-François Mosnier. CHU Hôtel Dieu, Nantes, France; analysis would be an important next step in evaluating the role of ErbB3 in CRC Faculté de Médecine, Nantes, France. prognosis. Increased expression of ErbB3 at the protein level in particular merits further Background: PD-1/PD-L1 blockade showed therapeutic effi cacy in only microsatellite study as a possible prognostic indicator in colorectal cancer. (MSI) colorectal carcinomas (CRC), however, the profi le of PD-L1 and PD-1 expression in CRC is only partially described. Design: We thus analyzed on FFPE whole-tissue sections of 80 CRC, the expression 644 Myosin 1e Expression Is Associated with Disease Progression profi le of PD-L1 by tumor and/or immune cells by immunohistochemistry (clone in Colorectal Cancer E1L3N) depending on the MSI status and the histological subtype, and correlated to Filippo Borri, Kodie Stem, Alessandro Bombonati, David Zuzga. Einstein Medical the density of PD-1+ and Tbet+ (able to secrete IFNg known to induce PD-L1) tumor- Center, Philadelphia, PA; La Salle University, Philadelphia, PA. infi ltrating lymphocytes (TIL). Background: Colorectal cancer (CRC) is the second leading cause of cancer-related Results: 78% of MSI CRC (32/41) overexpressed PD-L1 either by tumor or immune death globally. The current histopathological staging paradigm for identifying high-risk cells versus 46% of MSS CRC (18/39) (p 0.005). This overexpression was heterogeneous patients and predicting chemotherapy benefi t is imperfect. As a result, many patients within the same tumor in most of cases. Among MSI CRC, PD-L1 was preferentially are undertreated, putting them at increased risk for disease relapse, or overtreated, overexpressed in medullary carcinomas (MC, 19/21, 90%) compared with 65% exposing them to unnecessary and harmful chemotherapy with no potential benefi t. (13/20) in non medullary adenocarcinomas (p 0.06). PD-L1 expression by tumor cells ANNUAL MEETING ABSTRACTS 163A was only observed in MSI CRC (19/41, 46% with PD-L1 expression in more than with abnormal synaptophysin expression, altered distribution of ICC (CD 117) and 5% of tumor cells – score 1), and preferentially in MC (57% vs 5% in no medullary depleted SMA expression. These features were compatible with the clinical diagnosis adenocarcinomas, with PD-L1 expression in more than 50% of tumor cells – score 3, of myopathic type of intestinal pseudo-obstruction. p 0.0005). Conversely, PD-L1 expression by immune cells was observed in MSI CRC Conclusions: Adults presenting with symptoms of abdomen distension and chronic (23/41, 56% with PD-L1 expression by more than 5 sheets of 50 positive cells) but constipation should be evaluated for HD and its variants. Syndromic (MEN2B) and also in MSS CRC (18/39, 43%) (p 0.5). The density of PD-1+ cells was significantly autoimmune eitiologies should be kept in mind. Myopathic causes should be evaluated correlated to the PD-L1 expression, as well as the density of Tbet+ TIL. with a full thickness colonic biopsy. Unlike HD, surgical excision of the abnormal bowel Conclusions: PD-L1 expression is 1) heterogeneous in CRC, among CRC but also is not advocated as its proximal extent of the pathology is not assessable and hence the within the same tumor, 2) preferentially observed in MSI CRC (78%), especially in management is a challenge. MC (90%), where PD-L1 is expressed by tumor cells, 3) correlated with the density of PD-1+ or T-bet+ TIL, and 4) observed in a significant proportion of MSS CRC 649 Unique Prognostic Significance of CD206 and CD163 (46%) by immune cells only. From a clinical point of view, PD-L1 expression has to Macrophage Subtype Markers in Esophageal Adenocarcinoma be determined at best in full tissue section and besides its preferential expression in Wenqing Cao, Margaret A Black, Jiangzhou Yu. New York University Langone Medical MSI CRC, its significant frequency and expression profile (only by immune cells) in Center, New York, NY; University of Illinois at Chicago, Chicago, IL. MSS CRC should be taken into account in the future clinical trials testing the efficacy Background: Detection macrophage subtype in tumor microenvironment could be of anti-PD-1/PD-L1 antibodies. prognostically useful. M2 macrophage markers may be tissue specific. CD163 and CD206 are often used in a variety of tumors to correlate M2-like macrophage in tissue 647 Frequency of Deficient Mismatch Repair (MMR) Proteins and with patient prognosis. Thus we compared the prognostic significance of CD163 or HNPCC in Patients with Colorectal Carcinoma (CRC) Younger and Older CD206 positive M2 macrophage in esophageal adenocarcinoma (EAC). Than or Equal to 70 Years Design: EAC cell line SKTG was used to polarize THP1 monocyte into M2 macrophage. Azore-Dee Bradshaw, Margaret Cho, Gabriel Acosta Gonzalez, Richard A Hickman, RT-PCR was employed to identify its cytokine expression profile. 53 EAC resection Ruliang Xu. New York University Langone Medical Center, New York, NY. specimens were immunostained with CD68, CD163 and CD206. Average numbers of Background: The 2015 NCCN guidelines recommend screening either all CRC M2 (CD68+/CD163+) or (CD68+/CD206) macrophages were counted at five hot spots patients or those younger than 70 years old and those 70 years old and older who meet in tumor islet and tumor stoma, and correlated with clinicopathological factors. The the Bethesda guidelines for HNPCC at the time of diagnosis. It is debatable whether association between M2 macrophage and overall survival was analyzed using Kaplan- patients 70 years and older with colorectal cancer are less likely to have HNPCC. We Meier method. Other data analysis was done with Student t-test. analyzed the frequency of MSI-high status and HNPCC among these two groups of Results: M2 like macrophage induced by EAC cancer cell expressed high levels of patients to address this issue. CD163 and CD206. In EAC tissues, CD206 or CD163 positive cells were seen in tumor Design: We retrospectively searched our pathology database for patients who underwent islet and stroma. Compared to EACs without lymph node metastasis, CD206 or CD163 resection, polypectomy and biopsy for CRC from 2013 to 2016. Patient age, gender, positive M2-like macrophage counts in tumor islet and tumor stroma was not obviously tumor site, immunohistochemistry (IHC) result for MMR proteins, and HNPCC status increased in EACs with positive lymph nodes, and did not show a correlation with were recorded. IHC for MMR proteins was performed using Ventana kit (MLH1, lymph node metastasis. Interestingly, CD163 positive M2-like macrophage possessed MSH2, MSH6 and PMS2) and an automated system. Patients who only had MLH1 and a strong correlation with patient survival independent of location (p<0.05). Counts of PMS2 deficiency with positive BRAF mutation and hypermethylation were defined as CD206- or CD163-like macrophage in EAC was not associated with patient age, gender, low probability of HNPCC, whereas those who had either loss of PMS2 only, MSH2 tumor size, and tumor differentiation. and/or MSH6 were classified as high probability of HNPCC. Fisher’s exact test was Conclusions: CD163 is a suitable M2-like macrophage maker for macrophage subtype performed when appropriate. contributing to EAC progression and prognosis. Data also suggest choosing appropriate Results: Among 316 patients identified, 191 patients were <70 years old, and 125 M2 macrophage marker is important in related cancer studies. patients were >/=70 years old. Both groups had almost equal sex distribution (M:F ratio: 1.17:1 and 0.87:1). In the younger age group, the tumor was predominantly left-sided 650 Epidemiologic Evaluation of Biopsies Performed for Potential (n=137, 71%), whereas the older age group showed an equal distribution (n=62 vs. Gastrointestinal GVHD n=63). The percentage of loss of MMR proteins detected by IHC in the younger group David Carr, Grace Y Lin, Mojgan Hosseini. UC San Diego, San Diego, CA. (19% or 36/191) was not significantly different from that in the older age group (23% Background: Gastrointestinal graft-vs-host disease (GVHD) is an important or 29/125) (P>0.05). There was also no significant difference between the percentage complication of allogeneic bone marrow transplantation and is common in both its of patients with high probability of HNPCC in younger and older age groups (8% or acute and chronic forms. Severe gastrointestinal GVHD is an important diagnostic 16/191 vs. 2% or 3/125). However, among the patients with loss of MMR proteins in the entity associated with high mortality. With the incidence of bone marrow transplantation tumor, the younger age group had a significantly higher percentage of high probability increasing, and continued improvement in GVHD prophylactic regimens, a thorough of HNPCC (44% or 16/36 vs. 10% or 3/29) (P < 0.05). understanding of the presentation and epidemiology of GVHD is crucial. Conclusions: In our institution, screening by IHC for MMR proteins identified similar Design: The pathology archives were searched for gastrointestinal biopsies performed percentages of HNPCC or highly probable HNPCC in younger and older than 70 year for evaluation of GVHD from 2011-2015. Cases were reviewed and classified based old patient groups, supporting universal screening for HNPCC regardless of age. on NIH recommended diagnostic categories for GVHD (Negative for GVHD, Possible There is a higher percentage of HNPCC or highly probable HNPCC among patients in GVHD, and Likely GVHD). Clinical charts were reviewed for relevant data such the younger group who have loss of MMR proteins in the tumor, suggesting that the as transplant indication, transplant type, time since transplant, endoscopic findings, loss of MMR proteins in tumors in older patients is more likely an epigenetic event. clinical symptoms, prophylactic regimen, GVHD in other organs, and infectious status. Results: A total of 124 cases were identified. 54% of cases (67/124) were negative for 648 Hirschsprung Disease and Its Mimickers: A Detailed GVHD. 9% of cases (11/124) were considered possible GVHD. 37% of cases were Histomorphological Study of 12 Cases considered likely GVHD (46/124) of which 28% were grade 1, 24% grade 2, 22% grade Maria Bukelo, Amanda C Pinto, Suravi Mohanty, P Divya, N B Nandeesh, K M Babu, 3, and 26% grade 4. Of the negative cases, 12% (8/67) were due to infectious causes Usha Kini. St. John’s Medical College, Bengaluru, Karnataka, India. (CMV, EBV, adenovirus and C. difficile), one case was attributed to mycophenolate Background: Hirschsprung disease(HD) most commonly presents in neonates with toxicity, and the majority (87%; 58/67) had no specific diagnostic alteration. 27 of abdomen distension and constipation. Their rectal biopsy shows aganglionosis with 46 patients (59%; 95% CI [52, 66]) with a diagnosis of likely GVHD were deceased the presence of hypertrophic nerve bundles (HNBs). However, there are many adults at the time of chart review compared with 16 of 78 patients (21%; 95% CI [16-25]) who clinically resemble HD despite the presence of ganglion cells(GCs) in their rectal categorized as either likely GVHD or negative for GVHD (p < .001). biopsies. Various terms have been used to describe these conditions such as ‘variants of Conclusions: In this study, biopsies clinically suspicious for gastrointestinal GVHD HD’, ‘pseudo-HD’ or ‘chronic idiopathic pseudo-obstruction’. This study is aimed at a were reviewed. We found a significant difference in mortality between patients with a histomorphological evaluation of biopsies from adults who clinically presented as HD. positive GVHD biopsy of any grade compared to those with possible GVHD or negative Design: A retrospective 5 year histomorphological study of adult patients who presented biopsies. Overall, there was a relatively high positive biopsy rate for GVHD distributed with clinical features of Hirschsprung disease and no intestinal luminal pathology was over the spectrum of severity. Of the negative cases, a minority were attributed to done from our biopsy records. infectious etiologies (12%), however, the majority did not have any specific diagnostic Results: 12 adults aged between 21 and 55 years (mean age: 35 years) were selected. alterations. In conclusion, we find a significant association between a diagnosis of GVHD All 12 presented with abdominal distension and chronic constipation and 9 had a of any grade and increased mortality. The positive biopsy rate is relatively high when colostomy at some point in life. Frozen rectal mucosal biopsy in 10 patients showed there is clinical suspicion of gastrointestinal GVHD. Although infectious causes are an one case of HD (21 year/male) with aganglionosis & increased Acetylcholine Esterase important consideration, the majority of negative biopsies will fail to yield a definitive (AChE) activity; 5 cases with GCs and no HNBs, reported as 1. Normal innervation, diagnosis of other possible causative entities. 2. Hypoganglionosis, 3. Ganglioneuromatosis (Met918Thr mutation in exon 16 of the RET, confirmatory of MEN2B syndrome), 4. Lymphocytic ganglionitis and 5. 651 Examination of Lymph Node Status in Gastroenteropancreatic refractory constipation with associated megarectum. One of 2 cases with GCs and Neuroendocrine Tumors prominent nerve bundles had a megacolon secondary to Pheochromocytoma while the Luis Carrillo-Polanco, Peter N Bonneau, Christopher Hartley, Catherine Hagen. other had minimal chronic inflammation probably due to an inflammatory pathology. Medical College of Wisconsin, Milwaukee, WI; University of Wisconsin Hospital and Two cases with neither GCs nor HNBs with normal AChE activity were reported as Clinics, Madison, WI. normal innervation. Two cases did not have a rectal biopsy; the appendix in one showed Background: Presently, AJCC lymph node staging for gastroenteropancreatic (GEP) GCs and neuromatosis confirmed by IHC, while in the other, a full thickness colonic neuroendocrine tumors (NET) is classified as N0 (no lymph node metastases) or N1 (any biopsy showed the inner layer of muscularis propria with vacuolar change and atrophy lymph node metastases). In addition, previous studies have demonstrated examination of 164A ANNUAL MEETING ABSTRACTS fewer than 12 lymph nodes in colonic adenocarcinoma cases is associated with a worse 653 Dysplasia in Sessile Serrated Polyps Is Frequently Encountered prognosis; this concept has not been explored in GEP NETs. The goal of this study was in Patients Meeting Serrated Polyposis WHO Diagnostic Criteria to determine if the number of examined lymph nodes or the number of positive lymph Romulo Celli, Joanna Gibson. Yale Medical School, New Haven, CT. nodes is associated with prognosis in GEP NET. Background: Serrated polyposis syndrome (SPS) is defined by multiple colonic serrated Design: Our pathology database was searched from 2008-2013 for cases of GEP NET polyps (SP) and increased risk of colorectal cancer (CRC). The 2010 WHO criteria for with a corresponding lymph node dissection. Tumor characteristics including number SPS are: 1) >5 SP proximal to sigmoid with >2 being >1 cm; 2) any SP proximal to of lymph node metastases and number of lymph nodes examined were collected from sigmoid in a patient with a 1st-degree relative with SPS or 3) >20 SP. SPS incidence corresponding pathology reports. Patient outcome data was collected from chart review. is unknown and a confirmatory test is unavailable. We tested the utility of the WHO Results: The study group consisted of 84 GEP NET from an equal number of patients criteria in identifying patients with SPS in a large cohort. (38 small bowel/ampullary NET, 33 pancreatic NET (PanNET), 9 colorectal NET, 2 Design: 2345 consecutive patients with at least 1 SP (hyperplastic polyp, HP; sessile gastric NET, 2 appendiceal NET). The average number of lymph nodes examined per serrated polyp, SSP; and traditional serrated adenoma, TSA) were identified via case was 17.8 (range 1-66), the average number of positive lymph nodes per case was retrospective review of the pathology database over the year 2014. Each patient was 2.4 (range 0-18), and the average lymph node ratio per case was 0.19. PanNET had screened for SPS and clinicopathologic examination was performed of patients meeting significantly more lymph nodes examined per case compared to other sites (mean 22.6 WHO criteria. vs. 14.6, p=0.002) but the lymph node ratio for PanNET was not significantly different Results: We identified 32 patients (18 female, mean age 67 years) who met SPS WHO (0.15 vs. 0.22, p=0.22). When all cases were included, disease free survival was not criteria. 3 patients met criteria at the 1st colonoscopy; remaining patients met criteria significantly different for cases with <12 lymph nodes examined compared to those with after tabulating data from a mean of 3.5 procedures. 20 patients met criterion 1 (Group ≥12 lymph nodes examined (p=0.90). Using the current AJCC staging criteria, there was A), 7 met criterion 3 (Group B), and 5 met both 1 and 3. The mean number, size, some separation of patients with no lymph node metastases versus those with lymph anatomic distribution and histologic type of SP differed significantly between Group node metastases on survival curves, although not significant (p=0.37). When positive A and B (10.5 vs 30.4, p=0.00; 0.77 cm vs 0.41 cm, p=0.00, 29% vs 6% right sided, lymph nodes were divided into 1 or >1, this separation became less pronounced (p=0.53). p=0.00; and 39% vs 16% SSP, p=0.00, respectively). 13% of SPS patients had SSP with advanced neoplasia (SSP-AN), including 1 with high grade dysplasia and 3 with CRC , compared to 0.9% of the non-SPS patients in this cohort. The mean number of polyps in patients with SSP-AN was 23, and no patient with SSP-AN had less than 10 polyps. Conclusions: We identified 32 patients meeting SPS criteria among 2345 patients with at least one SP (1.4% incidence). SP histology, size and anatomic distribution varied between patients meeting criterion 1 or 3, confirming others’ findings of 2 SPS phenotypes and validating WHO criteria for identifying both. We did not identify patients meeting criterion 2, a limitation of our study design. 13% of SPS patients had SSP-AN, supporting the increased risk of neoplastic progression in patients with Conclusions: In these preliminary findings there is no evidence to suggest that the SPS compared to patients without SPS. Most patients met SPS criteria after 2 or more number of lymph nodes examined or number of positive lymph nodes are associated colonoscopies, and SSP-AN occurred in SPS patients with greater number of SP. Our with disease free survival for GEP NET. We are building a larger cohort to strengthen studies also suggest that SSP-AN may be an additional criterion for diagnosis of SPS. our findings. We recommend pathologists routinely reviewing prior pathology and medical records of patients with a diagnosis of any SP, including dysplastic SSP, to screen for SPS. 652 Clinical Significance of Monoclonal T-Cell Populations in Duodenal Lymphocytosis: Celiac and Non-Celiac Patients 654 Interobserver Variability in the Diagnosis of Inflammatory Bowel Romulo Celli, Pei Hui, Sidney Bogardus, Marie Robert. Yale Medical School, New Disease-Associated Dysplasia by International Telepathology Haven, CT. Michael Chang, Yanfei Huang, Dipti M Karamchandani, Xian-rui Wu, Daniela Allende, Background: Refractory Celiac disease (RCD) is defined as persistent duodenal villous John R Goldblum, Shu-Yuan Xiao, Hongfa Zhu, Michael Feely, Amy Collinsworth, blunting despite a gluten-free diet (GFD). Monoclonal T-cells in duodenal mucosa Ashwini K Esnakula, Hao Xie, Xiuli Liu. U of Florida, Gainesville, FL; Penn State U, in RCD is a criterion for RCD type II, portending a risk for enteropathy associated Hershey, PA; Sun Yat-sen U, Guangzhou, China; Cleveland Clinic, Cleveland, OH; U T-cell lymphoma (EATL). T-cell receptor (TCR) gene rearrangement by PCR using of Chicago, Chicago, IL; Mount Sinai Hosp, New York, NY; Yale U, New Haven, CT. paraffin-embedded tissue is a highly sensitive methodology, which may detect clinically Background: Dysplasia arising in association with inflammatory bowel disease (IBD) insignificant clones. No studies have evaluated the specificity of monoclonal TCR gene is the most significant marker of increased colorectal cancer risk in IBD patients. status in non-RCD duodenal lymphocytosis. We assessed T-cell clonality status and Telepathology (TP), the practice of remote diagnostic consultation, has seen increased clinical outcome in patients with RCD, celiac disease (CD) and Helicobacter pylori use nationally and internationally. The aim of this study was to evaluate the utility and (HP) associated duodenal lymphocytosis. interobserver variability of diagnosing dysplasia in IBD with TP. Design: Duodenal biopsies from 12 RCD patients, 11 CD patients and 5 patients with HP Design: Eight gastrointestinal (GI) pathologists were involved in this study. A total associated duodenal lymphocytosis were identified in our files. TCR gene rearrangement of 50 colonic biopsies from patients with IBD were included. One representative analysis was performed by PCR. Clinical follow up was obtained. microscopic slide in each case was digitized using an Aperio system. Photographs Results: Clonal TCR gene rearrangement was detected in 6/12 RCD (50%), 2/11 of the full slide images were captured at low, medium, and high magnifications at a untreated CD (18%), and 2/5 HP patients (40%). 2 RCD patients had identical clones in resolution of 1712 x 1072 pixels and saved as tagged image file format (TIFF) files on sequential biopsies. In sequential biopsies from 5 RCD patients, multiple different clones read-only DVD. Each pathologist selected the most appropriate diagnostic category were found. In RCD group: 2/12 patients died of disease, 3 require imunosuppression, for each case; a consensus diagnosis was defined as diagnostic agreement by at least 2 are entering clinical trials, 5 take supplements. None developed EATL; 1 developed 4 pathologists and included negative (n=22), low-grade dysplasia (n=22), high-grade nodal B-cell lymphoma; 2 developed small bowel carcinoma (mean follow up 6.5 dysplasia (n=3), cancer (n=2), and indefinite (n=1). A kappa coefficient analysis was years, range 0-20). Of 2 untreated CD patients with positive TCR, 1 improved on performed to determine interobserver agreement and the agreement of each pathologist GFD; one had persistent disease, with uncertain GFD status. The HP infected patients with the consensus diagnosis. had no malabsorption. Results: There was moderate interobserver agreement among 8 pathologists (kappa Table 1.Clonal TCR and Follow Up value 0.58 [0.50,0.67]). Agreement of each pathologist with the reference consensus New CD HP diagnosis revealed kappa values ranging from 0.53 to 0.84. RCD (n=12) (n=11) (n=5) Reviewer number Practice experience (years) Kappa Agreement Mean Age (yrs) 62 42 47 1 <5 0.53 Moderate 4 Gender (female, %) 9 (75%) 8 (73%) 2 <5 0.70 Substantial (80%) 3 <5 0.75 Substantial 2 TCR, clone (n, %) 6/12 (50%) 2 (18%) (40%) 4 <5 0.64 Substantial Sequential TCR (n=7) 2 5 >8 0.84 Almost perfect 5/7 2 (18%) Multiple Clones (40%) 6 >8 0.74 Substantial Persistent identical clone 2/7 0 0 7 >8 0.84 Almost perfect Development of Malignancy 2 Small bowel carcinoma 8 >8 0.81 Almost perfect (17%) 0 0 (n, %) 1 nodal B cell lymphoma (8%) GI pathologists with more than 8 years of practice experience achieved greater agreement with each other than those with less than 5 years of practice experience (kappa 0.69 Conclusions: Monoclonal T-cell populations are present in patients with RCD, newly vs. 0.50, respectively, p < 0.001). diagnosed CD, and HP associated duodenal lymphocytosis. This finding highlights Conclusions: This pilot study reveals moderate interobserver agreement on the the clinical non-specificity of results of PCR TCR gene rearrangement using paraffin interpretation of colonic dysplasia in IBD using digitized images. Greater practice embedded tissue. Test results should be correlated with morphology, sequential biopsies, experience seems to improve interobserver agreement. This study supports the efficacy and clinical status. The finding of monoclonal T-cell populations in conditions of of international consultation by digital pathology. duodenal lymphocytosis is of limited clinical significance as a stand-alone test. ANNUAL MEETING ABSTRACTS 165A 655 Hydrophilic Polymer Associated Ischemic Enterocolitis was 6.2 cm in mucinous variant which was similar (6.0 cm) in the conventional group Jesus A Chavez, Wei Chen, Wendy L Frankel, Christina A Arnold. The Ohio State (p > 0.05). Majority patients with mucinous iCC (83%) presented as at least stage T3, University, Columbus, OH. compared to 28% in the conventional group (p < 0.05). Follow-up study showed 3 Background: Hydrophilic polymer coating of medical devices serves to lubricate the patients with mucinous variant (50%) died of disease (0-1 year) with 1-year survival device and prevent device-related complications. The coating can be disrupted and rate of 17% compared with 26% of the conventional group. The average survival time result in downstream pathology via presumed thromboembolism. This process has of patients with mucinous iCC was significantly reduced compared to the conventional been reported in the brain, heart, lung, and skin, and has been replicated through animal group (0.17 vs 2 years; p < 0.05). Compared with 6 conventional iCC cases with studies and in vitro histologic processing of the polymer coating. We report the first matched age, sex and tumor stage , immunohistochemical analysis revealed positive description of hydrophilic polymer associated ischemic enterocolitis. immunoreactivity in MUC1 (83% vs 33%), MUC2 (29% vs 0); MUC5AC (86% vs Design: Prospective identification of the polymers from gastrointestinal resection 67%), MUC6 (43% vs 0), CK7 (71% vs 67%), CK20 (0 vs 33%), and CDX2 (14% specimens from 04/29/2014-08/08/2016 resulted in collection of seven specimens vs 0) in mucinous and conventional iCCs, respectively. Immunohistochemistry for (small bowel=2, colon=4, aortic thrombus=1) from three patients. PMS2 and MSH6 showed intact nuclear staining in all iCC cases, including mucinous Results: We report a 4% incidence of hydrophilic polymer associated ischemic variants. P53 showed 66% immunoreactivity in both mucinous and conventional groups. enterocolitis among all patients with an ischemic bowel resection during this study. Conclusions: Mucinous variant constitutes 7.4% of primary iCCs. Immunophenotypically, All patients developed bowel ischemia within one day of aortic repair. All resection mucinous variant is reactive for MUC1, MUC2 and MUC6 that is devoid in the specimens showed ischemia, and the polymers were mainly located in the submucosal conventional type. Unlike gastrointestinal mucinous adenocarcinoma, mucinous vessels in areas of ischemia. They appeared as intravascular, serpiginous structures with variant of iCCs are often CK7+/CK20- and microsatellite stable. Mucinous iCCs basophilia. In the patient who developed acute paralysis after the aortic repair, identical likely present at advanced stage upon diagnosis with worse prognosis compared to the polymers were identified in the aortic thrombus and the ischemic bowel segment. We conventional counterparts. demonstrate that the polymers display an altered morphology over time and with various graft types, and that the degrading polymers are associated with foreign body giant cell 658 Mast Cells in Microscopic Colitis: A Potential Therapeutic reaction. Special stains can be helpful with the polymers turquoise on a colloidal iron, Target? pink on a von Kossa and mucicarmine, and pale blue on a trichrome. Clinical follow-up Zhikai Chi, Romil Saxena. Indiana University School of Medicine, Indianapolis, IN. was available up to 115 weeks: one patient died, and the other two are alive and well. Background: Corticosteroids form the mainstay of therapy for microscopic colitis in Conclusions: In summary, we report a new diagnostic entity to be considered in patients with severe symptoms. However, the relapse rate is considerably high when the differential of iatrogenic ischemic injuries. Awareness of this entity is important therapy is discontinued. Long term steroid therapy, on the other hand predisposes to to elucidate the cause of ischemia and to prevent misdiagnosis of the polymers and steroid dependence and significant side effects. Identification of specific targets and their associated giant cell reaction as a parasitic infection, granulomatous vasculitis, alternate directed therapies is therefore highly desirable. sarcoidosis, and idiopathic inflammatory bowel disease. Design: Colonic biopsies of collagenous colitis (n=29) or lymphocytic colitis (n=35) were identified. Twenty colonic biopsies with no pathologic change served as controls. 656 Assessment of PD-L1 Expression in Tumor Microenvironment Immunohistochemistry for tryptase was performed in all cases. Number of mast cells of Mismatch Repair Deficient Colon Cancer: Comparing Two Antibody in lamina propria, muscularis mucosae and submucosa in fields with the highest and Clones, SP142 vs. SP263 lowest density were counted. Presence of extracellular tryptase was recorded. The Zongming E Chen, Angela Bitting, Fan Lin. Geisinger Medical Center, Danville, PA. number of fragments that showed inflammation were counted in each case to assess Background: Mismatchrepair deficient (MMRD) colon cancer harbors increased the extent of inflammation. number of somatic mutations and is potentially more immunogenic. To evade host Results: immune destruction, the tumor cells utilize check point inhibition mechanisms. Lymphocytic Collagenous Controls Consequently, PD-L1 expression in the tumor microenvironment exhibits prognostic colitis (n=35) Colitis (n=29) (n=20) significance in this subtype; and majority patients benefit from anti-PD1 immunotherapy. Age (mean, range) 69 (45-93) 68 (49-89) 61 (52-93) However, the evaluation of PD-L1 expression may differ depending on different antibody clones. Here, we compared the results using two PD-L1 clones SP142 and Females (%, n) 68% (24) 90% (26) 70% (14) SP263. Lamina Propria 30 (13-42)** 39 (19-63)*** 23 (10-37) Design: Immunohistochemistry (IHC) for PD-L1 was performed on 40 MMRD colon Highest count per Muscularis high power field 1 (0-3) 1 (0-3) 1 (0-1) adenocarcinomas using tissue microarray sections. The tumors were selected for their Mucosae (mean, range) lack of MLH1 and PMS2 expression by IHC and positive for BRAF V600E mutation. Submucosa 12 (3-26) 15 (4-37) 10 (3-22) Two PD-L1 antibodies (clones SP142 and SP263, Ventana, AZ, USA) were optimized Lamina Propria 17 (6-27)** 20 (8-45)** 12 (3-25) according to the vender’s protocols and used in assays. A four-tiered grading system was Lowest Count Muscularis used for evaluating PD-L1 expression on immune and tumor cells, respectively (Table per high power 0 (0-1) 0 (0-1) 0 (0-1) Mucosae 1). Statistical analysis was performed using two-tailed Fisher exact test. field(mean, range) Submucosa 7 (0-21) 8 (1-25) 6 (3-11) Results: A significant PD-L1 expression was detected in the tumor microenvironment by both antibodies (Table 1). However, the detection sensitivity for tumor cells was Extracellular tryptase present (%, n) 60% (21)*** 41% (12)* 10% (2) significantly lower using SP142 compared to SP263, particularly in low level of % of inflammed fragments (range) 89% (44-100) 93% (63-100) ecxelplrse bsesetwrse. eAnl tthhoeu tgwho n aon sttiabtoisdtiiecsa,l liyn dmifofesrt ecnats iens ,d tehteec etvinaglu PaDtio-Ln1 a enxdp srceossriionng iwn aims emasuineer Mpeer ahni ghhig phoewste cr ofiuenldt <fr8a0g%me inntflsammed 22 (13-30; n=8) 4559 ;(n3=14-)*** using SP142 in the absence of interference from coexisting tumor cell staining pattern. in lamina propria >80% inflammed 32 (17-42; 38 (19- Stromal and intratumoral immune cells Tumor cells (range) fragments n=27)** 63;n=25)** Antibody 40 tumors in total 40 tumors in total clones *p<0.05, **p<0.01, ***p<0.001 <1% 1-5% >5% <1% 1-5% >5% Conclusions: The pathogenesis of microscopic colitis is largely unknown and likely to SP142 12 3 25 34 3 3 be multifactorial; our findings suggest that mast cells may play a role. SP263 10 10 20 17 12 11 Therapies targeting mast cells, especially those that stabilize cell membranes and prevent degranualtion, may be effective in these patients, thus precluding the need for *p-value N/A 0.80 .37 N/A 0.01 <0.01 long term steroid therapy. *Note: p-value was calculated for each bracket as if the lowest percentage is used as potential Evaluation of mast cell numbers, presence of extracellular tryptase, and extent of positive cutoff value. inflammation might identify patients most likely to respond to such therapies. Conclusions: PD-L1 expression is upregulated in tumor microenvironment of MMRD colon cancer. Depending on the choice of specific antibody clones, significant difference 659 Programmed Cell Death-Ligand 1 Expression in Microsatellite may exist in the evaluation of PD-L1 expression in tumor and immune cells. This Instability-High Gastric Carcinomas variation should be considered when applying PD-L1 expression as a prognostic or Junhun Cho, Young Hwan Chang, Hyunsik Bae, Kyoung-Mee Kim. Soonchunhyang predictive biomarker for clinical use. University Cheonan Hospital, Soonchunhyang University College of Medicine, Cheonan, Korea; Oregon Health & Science University, Portland, OR; Samsung Medical 657 Mucinous Variant of Intrahepatic Cholangiocarcinoma: A Center, Sungkyunkwan University School of Medicine, Seoul, Korea. Clinicopathological and Immunochemical Study Background: Programmed death-ligand 1 (PD-L1) is expressed in a subgroup of Zhikai Chi, Amarpreet Bhalla, Hanlin L Wang, Deepa T Patil, Jingmei Lin. Indiana gastric cancer(GC) that may benefit from immunotherapy. Microsatellite instability- University School of Medicine, Indianapolis, IN; University of California David Geffen high (MSI) is a potential predictive factor for the response of immune therapy targeting School of Medicine, Los Angeles, CA; Robert J. Tomsich Pathology and Laboratory PD-1/PD-L1. However, the interaction between PD-L1 expression and MSI remains Medicine Institute, Cleveland, OH. poorly understood. Background: Mucinous variant of intrahepatic cholangiocarcinoma (iCC) is not Design: We investigated PD-L1 expression in 78 MSI GC tissues using common. The clinicopathological features and prognosis are far less clear. immunohistochemistry. Design: Six patients who had iCCs with more than 50% of mucinous differentiation Results: Based on PD-L1 expression status, we classified PD-L1 expression cases were included in the study that was compared to 81 cases of conventional iCCs. into tumor cell (PD-L1TC+/-) and immune cell (PD-L1IC+/-) expression by pathologic Results: The mean ages in mucinous and conventional iCC groups were 59 (range, examinations and the results were compared to those of digital automatic quantifications 40-82) and 61 (range, 52-82), respectively (p > 0.05). The female to male ratio was 0.5 using acquired images with an Aperio slide scanner. Each stain was artificially in mucinous group compared to 1.4 in conventional iCC (p > 0.05). The size of tumor attributed a color code, and images were overlaid using ImageJ. Pixel colocalization 166A ANNUAL MEETING ABSTRACTS was assessed by calculating Manders’ overlap coefficient with threshold set by Costes Design: DNA flow cytometry was performed using FFPE tissue from 78 high grade method (tM) using Fiji (Coloc 2 plug-in). We perform cell segmentation using Otsu’s dysplasia (HGD) (36 biopsies, 42 resections), 14 low grade dysplasia (LGD) (11 method and define PD-L1 positive cell ratio as an absolute number of positive cells biopsies, 3 resections), and 9 BE without dysplasia. Three to four 60 micron thick per square millimeter. With pathologic observation, we observed PD-L1 expression in sections were cut from each block, and area of interest was dissected for analysis. 48 (61.5%) cases consisting 7 (9.0%) PD-L1TC+ and 47 (60.3%) PD-L1IC+. PD-L1IC+ Results: DNA content abnormality (aneuploidy and/or elevated 4N fraction) was was frequently associated with higher lymph node metastasis (p=0.027) and advanced identified in 74 (95%) HGD, 5 (36%) LGD, and no BE case without dysplasia. The TNM stages (p=0.029). Moreover, PD-L1IC+ is an independent favorable prognostic DNA content abnormality was similar in biopsies (94%) and resections (95%) in HGD factor in overall survival (versus PD-L1IC-; hazard ratio, 3.451; 95% confidence interval, cases. Seventy-three percent of LGD cases with DNA content abnormality progressed 1.172-12.745; p=0.025). We found significant correlation between manual and automatic to HGD/EAC at 1 year, with 100% progression at 4 years (p = 0.037). By contrast, the quantifications (r =0.8 and P < 0.001, Spearman test) of PD-L1 positive cells. 1-year detection rate of HGD/EAC for LGD cases in the setting of normal DNA flow Conclusions: In MSI-high GC, PD-L1 expression in immune cells is independently cytometric findings was 17%, which remained unchanged at 12 years. The hazard ratio associated with longer survival. for subsequent detection of HGD/EAC for patients with DNA content abnormality detected at baseline LGD was 7.23 (p = 0.039; 95% confidence interval, 1.065-141.52). Conclusions: This study demonstrates the promise of flow cytometry using FFPE 660 IgG4-Related Disease of the Gastrointestinal Tract: A Tertiary tissue in the diagnosis and risk stratification of dysplasia in BE. The majority of HGD Care Hospital Experience cases (95%) show DNA content abnormality. LGD with DNA content abnormality is Woo Cheal Cho, Saverio Ligato, Richard Cartun, Anshu Trivedi. Hartford Hospital, at higher risk for progression to HGD/EAC. Hartford, CT. Background: IgG4-related disease (RD) is a newly recognized rare clinicopathologic No dysplasia HGD LGD (n=14) entity characterized by dense fibrosis & lymphoplasmacytic infiltration rich in IgG4- (n=9) (n=78) positive plasma cells in association with an elevated serum IgG4 level. We report our DNA content abnormality 0 (0%) 5 (36%) 74 (95%) 10-year experience with IgG4-RD as a tertiary care hospital, with a primary focus 73% (with abnormal DNA on the gastrointestinal tract, & discuss the challenges associated with the diagnosis. Progression to HGD/EAC content) – – Design: We searched our laboratory database for patients with suspected IgG4-RD at 1 year 17% (without abnormal DNA encountered over a 10-year period (2006-2016), using the following terms: “IgG4,” content) “autoimmune pancreatitis,” “autoimmune sclerosing cholangitis,” “retroperitoneal fibrosis,” and “inflammatory pseudotumor.” All slides and electronic medical records were retrospectively reviewed. 662 Gastric Pyloric Gland Adenoma: A Multicenter Clinicopathologic Results: The material examined consisted of 11 surgical and 5 biopsy specimens, Study of 65 Cases all of which were histologically confirmed to have IgG4-RD in at least 1 organ. 63% Won-Tak Choi, Ian Brown, Tetsuo Ushiku, Masato Yozu, Namrata Setia, Amitabh were male and the median age at diagnosis was 60.5 years (range, 15-79). The primary Srivastava, Melanie Johncilla, Rish K Pai, Masashi Fukayama, Joseph Misdraji, sites in order of frequency were as follows: pancreas (6), mesentery (5), bile duct (3), Gregory Y Lauwers. UCSF Medical Center, San Francisco, CA; Envoi Pathology, retroperitoneum (3), & gallbladder (1). Serum IgG4 levels were obtained in 19% Kelvin Grove Qld, Australia; University of Tokyo, Tokyo, Japan; Massachusetts General (3/16) of patients, all of whom were found to have elevated serum IgG4 levels. In 1 Hospital, Boston, MA; University of Chicago, Chicago, IL; Brigham and Women’s patient, a serum total IgG level was obtained instead, which was elevated at 1852 mg/ Hospital, Boston, MA; Mayo Clinic, Phoenix, AZ. dL. 13% (2/16) of patients had a history of malignancy and 6% (1/16) of patients had Background: Gastric pyloric gland adenoma (PGA) is a rare neoplasm known to occur another documented autoimmune disease. Of 6 patients with IgG4-related sclerosing in the setting of autoimmune gastritis (AIG), familial adenomatous polyposis (FAP), or pancreatitis, 33% (2/6) of them had a history of alcohol abuse. 13% (2/16) of patients Lynch syndrome. Although PGA may have a high malignant potential, it remains under- were treated with steroid alone or combination of steroid & immunosuppressive therapy. recognized, and there is limited information regarding its clinicopathologic features Of 2 patients who received treatment, 1 patient experienced a relapse. and risk factors for high-grade dysplasia (HGD) or adenocarcinoma. Conclusions: In our study, only a small portion of patients were further tested by Design: 65 PGAs from 56 patients were reviewed, and immunohistochemistry for serology & received treatment with steroid following tissue diagnosis. Although MUC6 (pyloric gland mucin marker) and MUC5AC (foveolar mucin marker) was histology remains the gold standard for the diagnosis of IgG4-RD, the complete spectrum performed. of histologic changes may not be seen, particularly in a biopsy specimen. Given the fact Results: PGA occurred more commonly in females (52%) with a mean age of 68. that IgG4-RD is steroid-responsive, increased awareness of this entity among clinicians It usually appeared as a polypoid lesion (80%) in the gastric body (48%) but also is crucial not only for accurate & timely diagnosis but also for proper management. presented as a mass (6%), dome-shaped lesion (5%), or nodule (3%) in other parts of stomach: fundus (15%), cardia (8%), antrum (6%), or pylorus (3%). Among 45 PGAs with available background mucosa, 12 cases (27%) developed in a background of AIG; the remaining 73% was not associated with AIG, including 16 in normal mucosa (36%). Five patients (9%) had FAP. The average size of PGAs was 2.3 cm. Thirty-six of 65 cases (55%) showed low-grade dysplasia (LGD) with an average size of 1.7 cm, while 24 cases of HGD (37%) were larger (average 3.4 cm) including 8 cases (33%) with adenocarcinoma. Tubulovillous architecture was more common in HGD (52%) than LGD cases (33%). In contrast with other series that reported a predominant pyloric-type (MUC6+, < 30% MUC5AC+) as the most common phenotype, typically arising in a background of AIG, our series showed that the majority of PGAs (51%) coexpressed MUC5AC with MUC6 in an intermixed pattern, followed by 24% of a predominant pyloric-type and 22% of a pure pyloric-type. PGAs with HGD and/or adenocarcinoma were more frequently associated with AIG (37%) compared to those with LGD (24%). Among 45 patients with known clinical follow-up, Only 3 patients (7%) had a recurrence within a year. Conclusions: PGA frequently demonstrates a combination of pyloric and foveolar epithelium and coexpresses MUC5A with MUC6 (mixed type). Many cases are not associated with AIG or a genetic syndrome. Although the occurrence of HGD and/or adenocarcinoma is increased with the size of the lesion and association with AIG and tubulovillous architecture, recurrence is low. 663 Concordance Between Mismatch Repair Status from Primary Colorectal Carcinoma and Distant Metastasis Lani K Clinton, Thomas Plesec. Cleveland Clinic, Cleveland, OH. 661 DNA Flow Cytometric Analysis of Barrett’s Esophagus-Related Background: Approximately 50-60% of colorectal cancer (CRC) patients develop Dysplasia Using Paraffin-Embedded Tissue: DNA Content Abnormality metastases; often these patients are not surgical candidates. In these stage IV CRC Can Serve as Both Diagnostic Marker of Dysplasia and Predictive Marker patients, DNA mismatch repair (MMR) status helps guide medical management. In a of Neoplastic Progression recent phase II clinical trial, patients with MMR deficient CRCs responded significantly Won-Tak Choi, Peter S Rabinovitch, Thomas Small, Danning Huang, Aras N Mattis, better to the anti-programmed death 1 (PD-1) inhibitor, pembrolizumab, than patients Sanjay Kakar. UCSF Medical Center, San Francisco, CA; University of Washington, with MMR competent tumors. However, there are very limited data on the concordance Seattle, WA; SUNY Upstate Medical University, Syracuse, NY. of MMR status between primary CRC and distant metastasis, which causes uncertainty Background: The diagnosis of dysplasia in Barrett’s esophagus (BE) can be challenging, regarding the best tissue to assess for MMR status. and reliable ancillary techniques are not available. Flow cytometry for DNA content Design: After IRB approval, we reviewed specimens from patients who underwent has been shown to be a good biomarker for predicting esophageal adenocarcinoma extended RAS testing (between 3/14-8/16), indicating stage IV disease. Initial MMR (EAC). These studies have used fresh tissue, which is difficult in routine practice and testing was done by polymerase chain reaction (PCR), immunohistochemistry (IHC), does not allow correlation of morphologic findings with flow cytometry results. This or both. IHC for PMS2 and MSH6 was performed on the metastases, given the well- study examines the utility of DNA content analysis by flow cytometry in formalin-fixed established and robust correlation of PMS2 and MSH6 expression with MSI PCR status paraffin-embedded (FFPE) tissue in BE with dysplasia. and expression of all 4 MMR proteins by IHC.