Recent Results 123 in Cancer Research Managing Editors Ch. Herfarth, Heidelberg· H. -1. Senn, St. Gallen Associate Editors M. Baum, London . V. Diehl, K6ln F. Gutzwiller, Zurich· M.F. Rajewsky, Essen M. Wannenmacher, Heidelberg Founding Editor P. Rentchnick, Geneva Recent Results in Cancer Research Volume 113 U. Eppenberger, A. Goldhirsch (Eds.): Endocrine Therapy and Growth Regulation of Breast Cancer 1989.26 figures, 17 tables. IX, 92. ISBN 3-540-50456-7 Volume 114 P. Boyle, C.S. Muir, E. Grundmann (Eds.): Cancer Mapping 1989.97 figures, 64 tables. IX, 277. ISBN 3-540-50490-7 Volume 115 H.-J. Senn, A. Goldhirsch, R.D. Gelber, B. Osterwalder (Eds.): Adjuvant Therapy of Primary Breast Cancer 1989.64 figures, 94 tables. XVI, 296. ISBN 3-540-1881O-X Volume 116 K.W. Brunner, H. Fleisch, H.-J. Senn (Eds.): Bisphosphonates and Tumor Osteolysis 1989.22 figures, 6 tables. IX, 78. ISBN 3-540-50560-1 Volume 117 V. Diehl, M. Pfreundschuh, M. Loeffler (Eds.): New Aspects in the Diagnosis and Treatment of Hodgkin's Disease 1989.71 figures, 91 tables. XIV, 283. ISBN 3-540-51124-5 Volume 118 L. Beck, E. Grundmann, R. Ackermann, H.-D. Roher (Eds.): Hormone-Related Malignant Tumors 1990.83 figures, 91 tables. XI, 269. ISBN 3-540-51258-6 Volume 119 S. Briinner, B. Langfeldt (Eds.): Advances in Breast Cancer Detection 1990. 53 figures, 51 tables. XI, 195. ISBN 3-540-52089-9 Volume 120 P. Band (Ed.): Occupational Cancer Epidemiology 1990.23 figures, 59 tables. IX, 193. ISBN 3-540-52090-2 Volume 121 H.-J. Senn, A. Glaus (Eds.): Supportive Care in Cancer Patients II 1991. 49 figures, 94 tables. XIV, 465. ISBN 3-540-52346-4 Volume 122 W.J. Eylenbosch, M. Kirsch-VoIders, A. Deleener, J. Weyler (Eds.): Primary Prevention and Cancer 1991, 16 figures, 28 tables. IX, 130. ISBN 3-540-53704-X lW. Oosterhuis H. Walt I. Damjanov (Eds.) Pathobiology of Human Germ Cell Neoplasia With 48 Figures and 10 Tables Springer-Verlag Berlin Heidelberg New York London Paris Tokyo Hong Kong Barcelona Budapest Prof. Dr. J. Wolter Oosterhuis Dr. Daniel den Hoed Cancer Center Groene Hilledijk 301 NL-3075 EA Rotterdam, The Netherlands Dr. Heinrich Walt Department of Gynecology and Obstetrics Research Division of Gynecology University Hospital CH-8091 Zurich, Switzerland Prof. Dr. Ivan Damjanov Department of Pathology Jefferson Medical College Thomas Jefferson University 132 South 10th Street Philadelphia, PA 19107, USA ISBN -13: 978-3-642-84487 -4 e-ISBN -13: 978-3-642-84485-0 DOl: 10.1007/978-3-642-84485-0 This work is subject to copyright. All rights are reserved, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in other ways, and storage in data banks. Duplication of this publication or parts thereof is only permitted under the provisions of the German Copyright Law of September 9, 1965, in its current version, and a copyright fee must always be paid. Violations fall under the prosecution act of the German Copyright Law. © Springer-Verlag Berlin Heidelberg 1991 Softcover reprint of the hardcover 1st edition 1991 The use of registered names, trademarks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. Product Liability: The publisher can give no guarantee for information about drug dosage and application thereof contained in the book. In every individual case the respective user must check its accuracy by consulting other pharmaceutical literature. Typesetting: Best-set Typesetter Ltd., Hong Kong 25/3130-543210 - Printed on acid-free paper. Preface Germ cell tumors have been fascinating pathologists for decades. It was not until recently, however, that major advances in the chemotherapy of malignant germ cell tumors focused the attention of the entire medical community on these neoplasms. Once lethal for most patients, these tumors have become a prototype of successful chemotherapy. Basic scientists have become interested in the subject since the cloning and characterization of the cell lines of human germ cell tumors was introduced about 10 years ago. Primarily meant as tools to study human developmental biology, these cell lines are also employed to investigate the biology of human germ cell neoplasia. It is certain that students of human germ cell neoplasia have much to learn from developmental biologists, in par ticular those who use murine teratocarcinoma as models. The reverse is probably also true. To stimulate this mutual learning process, the symposium Pathobiology of Human Germ Cell Neoplasia was organized in August 1989, in Groningen, as a satellite meeting of the 11th Congress of the International Society of Developmental Biologists held in Utrecht. The present volume is based on this meeting and provides information to the public not directly concerned with research on germ cell tumors about the recent progress made in the field. The financial support of our sponsors is gratefully acknowl edged: 1.K. de Cock-Stichting, Groningen; Stichting Patho logisch Anatomisch Laboratorium, Groningen; Koninklijke Smilde B.Y., Heerenveen; The Netherlands Cancer Founda tion, Amsterdam; Stichting Kinderoncologie Groningen, Groningen; Stichting Werkgroep Interne Oncologie, Gronin- VI Preface gen; Nederlandse Middenstands Bank, Groningen; and Bri stol Myers, Weesp. We thank the authors for their excellent contributions to this book. The opportunity given to us by Professor E. Grundmann to publish the proceedings of the meeting in the series Recent Results in Cancer Research is highly appre ciated. Finally we thank Silwia Nijdam for her enthusiastic secretarial help. We hope that the readers of this volume may experience some of the excitement that was ours at the meeting in Groningen. 1. W. Oosterhuis H. Walt I. Damjanov Contents Overview........................................ 1 1. Damjanov Pathobiology of Human Germ Cell Neoplasia. . . . . . . . . 1 Cells of Origin. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 21 A. Giwercman, J. Muller, and N.E. Skakkebcek Carcinoma in Situ of the Testis: Possible Origin, Clinical Significance, and Diagnostic Methods. . . . . . . .. 21 H. Walt, P. Emmerich, A. Jauch, and CD. DeLozier-Blanchet Characterization of Precancerous and Neoplastic Human Testicular Germ Cells. . . . . . . .. 37 1. Vorechovsky and K. Mazanec Cytogenetic Investigation of Gonadal Carcinomas in Situ in Syndromes of Abnormal Sexual Differentiation . . . .. 45 Cell Lines ....................................... 51 M.F. Pera, S. Cooper, W. Bennet, and 1. Crawford-Bryce Human Embryonal Carcinoma and Yolk Sac Carcinoma in Vitro: Cell Lineage Relationships and Possible Paracrine Growth Regulatory Interactions. . .. 51 M.D. Mason and M.F. Pera Biochemical Analysis and Cellular Location of the GCTM-2 Antigen in Embryonal Carcinoma and in Other Tumour Cell Lines .................... 59 VIII Contents Differentiation Antigens 63 P. W. Andrews, 1. Marrink, G. Hirka, A. von Keitz, D. Th. Sleijfer, and E. Gonczol The Surface Antigen Phenotype of Human Embryonal Carcinoma Cells: Modulation Upon Differentiation and Viral Infection ................................... 63 F.E. von Eyben, O. Blaabjerg, P.H. Pertersen, S. Mommsen, E.L. Madsen, F. Kirpekar, S.S.-L. Li, and K. Kristiansen Lactate Dehydrogenase Isoenzyme 1 in Testicular Germ Cell Tumors. . . . . . . . . . . . . . . . . . . .. 85 P. Dniber Expression of Developmentally Regulated Genes in Embryonal Carcinoma Cells ..................... 93 Chromosomal Studies .. . . . . . . . . . . . . . . . . . . . . . . . . . .. 101 S.M.M.J. Castedo, l. W Oosterhuis, and B. delong Cytogenetic Studies of Testicular Germ Cell Tumors: Pathogenetic Relevance . . . . . . . . . . . . . . . . . . . . . . . . . .. 101 P. Dal Cin and H. Van Den Berghe Isochromosome (12p) in Germ Cell Tumors .......... 107 Molecular Genetics ............................... 113 A. Geurts van Kessel, R. Suijkerbuijk, B. de long, and l. W Oosterhuis Molecular Analysis of Isochromosome 12p in Testicular Germ Cell Tumors. . . . . . . . . . . . . . . . . . . .. 113 E. Dmitrovsky, E. Rodrigues, F. Samaniego, VE. Reuter, WH. Miller, lr., N.L. Geller, G.J. Bosl, and R.S.K. Chaganti Analysis of Chromosome 12 Abnormalities in Male Germ Cell Cancers ............................... 119 M.P. Mulder, W Keijzer, T.A. W Splinter, and1.L. Bos Frequent Occurrence of Activated ras Oncogenes in Seminomas but Not in Nonseminomatous Germ Cell Tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 125 Contents IX L. Bottero, A. Simeone, L. Arcioni, D. Acampora, P. W Andrews, E. Boncinelli, and F. Mavilio Differential Activation of Homeobox Genes by Retinoic Acid in Human Embryonal Carcinoma Cells. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 133 Growth Factors and Their Receptors. . . . . . . . . . . . . . . .. 145 W Engstrom, M. Tally, M. Granerus, E.P. Hedley, and P. Schofield Growth Factors and the Control of Human Teratoma Cell Proliferation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 145 E.J.J. van Zoelen Role of Heparin-Binding Growth Factors in Embryonic Tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 155 c.L. Mummery and S.M. Weima Growth Factors and Receptors During Differentiation: A Comparison of Human and Murine Embryonal Carcinoma Cell Lines ............ 165 WHo Miller, Jr. and E. Dmitrovsky Growth Factors in Human Germ Cell Cancer . . . . . . . .. 183 Subject Index .................................... 191 List of Contributors* Acampora, D. 1331 Gonczol, E. 63 Andrews, P.W. 63,133 Granerus, M.145 Arcioni, L. 133 Hedley, E.P.145 Bennet, W. 51 Hirka, G. 63 Berghe, H. Van Den 107 Jauch, A. 37 Blaabjerg, O. 85 Jong, B. de 101,113 Boncinelli, E. 133 Keijzer, W. 125 Bos, J.L.125 Keitz, A. von 63 Bosl, G.J.119 Kirpekar, F. 85 Bottero, L.133 Kristiansen, K. 85 Castedo, S.M.M.J.101 Li, S.S.-L. 85 Chaganti, R.S.K. 119 Madsen, E.L. 85 Cooper, S. 51 Marrink, J. 63 Crawford-Bryce, I. 51 Mason, M.D. 59 Dal Cin, P. 107 Mavilio, F.133 Damjanov, I. 1 Mazanec, K. 45 DeLozier-Blanchet, C.D. 37 Miller, W.H., Jr.119, 183 Dmitrovsky, E.119, 183 Mommsen, S. 85 Dniber, P. 93 Mulder, M.P. 125 Emmerich, P. 37 Miiller,J.21 Engstrom, W. 145 Mummery, C.L.165 Eyben, F.E. von 85 Oosterhuis, J.W.101, 113 Geller, N.L.119 Pera, M.F. 51, 59 Geurts van Kessel, A. 113 Petersen, P.H. 85 Giwercman, A. 21 Reuter, Y.E.119 * The address of the principal author is given on the first page of each contribution. I Page on which contribution begins.