GERM CELL TUMOR Edited by Angabin Matin Germ Cell Tumor Edited by Angabin Matin Published by InTech Janeza Trdine 9, 51000 Rijeka, Croatia Copyright © 2012 InTech All chapters are Open Access distributed under the Creative Commons Attribution 3.0 license, which allows users to download, copy and build upon published articles even for commercial purposes, as long as the author and publisher are properly credited, which ensures maximum dissemination and a wider impact of our publications. After this work has been published by InTech, authors have the right to republish it, in whole or part, in any publication of which they are the author, and to make other personal use of the work. Any republication, referencing or personal use of the work must explicitly identify the original source. As for readers, this license allows users to download, copy and build upon published chapters even for commercial purposes, as long as the author and publisher are properly credited, which ensures maximum dissemination and a wider impact of our publications. Notice Statements and opinions expressed in the chapters are these of the individual contributors and not necessarily those of the editors or publisher. No responsibility is accepted for the accuracy of information contained in the published chapters. The publisher assumes no responsibility for any damage or injury to persons or property arising out of the use of any materials, instructions, methods or ideas contained in the book. Publishing Process Manager Dragana Manestar Technical Editor Teodora Smiljanic Cover Designer InTech Design Team First published March, 2012 Printed in Croatia A free online edition of this book is available at www.intechopen.com Additional hard copies can be obtained from orders@intechopen.com Germ Cell Tumor, Edited by Angabin Matin p. cm. ISBN 978-953-51-0456-8 Contents Preface VII Part 1 Clinical Perspectives 1 Chapter 1 Intratubular Germ Cell Neoplasms of the Testis and Bilateral Testicular Tumors: Clinical Significance and Management Options 3 Nick W. Liu, Michael C. Risk and Timothy A. Masterson Chapter 2 Management of Nonseminomatous Germ Cell Tumor of the Testis 23 Paul H. Johnston and Stephen D.W. Beck Chapter 3 Diagnostic Imaging of Intracranial Germ Cell Tumors: A Review 47 Takamitsu Fujimaki Chapter 4 Testicular Germ Cell Tumours – A European and UK Perspective 59 Nikhil Vasdev and Andrew C. Thorpe Part 2 Scientific Perspectives 73 Chapter 5 Mouse Models of Testicular Germ Cell Tumors 75 Delphine Carouge and Joseph H. Nadeau Chapter 6 Epigenetic Modifications in Testicular Germ Cell Tumors 107 Christopher J. Payne Chapter 7 Claudins and Germ Cell Tumors 135 Ylermi Soini Preface In Germ Cell Tumor, leading scientists and physicians from different countries have contributed to review the latest ideas and developments regarding the clinical presentation, current treatment modalities and the biology and genetics of germ cell tumors. Most authors have focused on testicular germ cell tumors which are the most common cancers in young adult males and whose incidence has been increasing in recent years. The book is divided into two sections. The first section, Clinical Perspectives, discusses observations and current ideas regarding presentation and treatment of germ cell tumors in children and adults. Clinical perspectives includes a comprehensive review by Nick Liu and co-authors regarding the pathogenesis, risk factors, diagnosis and treatment regimens applied to intratubular germ cell neoplasia which are the precursor, pre-invasive lesion for testicular cancers. In Chapter 2, Paul Johnston and Stephen Beck review current management options for the most common type of germ cell tumors of the testes, non-seminomatous germ cell tumors. In Chapter 3, Takamitsu Fujimaki reviews intracranial germ cell tumors, which affect mostly children, and their diagnosis and treatment. Additionally, Chapter 4 reviews current management strategies for all the different histological sub-types of testicular cancers. Nikhil Vasdev and Andrew Thorpe provide a European perspective on treatment of germ cell tumors. In the second section, Scientific Perspectives, the chapters review current perspectives on experimental systems such as mouse models of testicular germ cell tumors and the genetics and epigenetics of germ cell tumor development in humans and in mice. Delphine Carouge and Joseph Nadeau provide a thorough review on mouse models of testicular germ cell tumors (Chapter 6). They also compare results obtained from genetic studies of testicular cancer susceptibility in humans to that in mice. Epigenetic dysregulation is implicated in a variety of cancers, including in testicular cancers. Christopher Payne presents an up to date review on the epigenetic modifications found in normal germ cells, in the pre-invasive precursor cells and in testicular germ cell tumors of young adults (Chapter 7). Yiermi Soini reviews the role of claudins, which are components of tight junctions, in germ cell tumors (Chapter 8). VIII Preface These chapters will be useful for scientists, physicians and lay readers wishing to review the current status of our knowledge regarding germ cell cancers. We hope that the chapters will serve to inspire further ideas towards increased understanding of development of germ cell cancers and improved treatment and management of this disease. I thank all the authors for their contributions. In addition, I thank Ms. Gorana Scerbe and Dragana Manestar for their invaluable assistance in the preparation and publication of this book. Angabin Matin U.T. M.D. Anderson Cancer Center, Houston, Texas USA [...]... encountered in patients with bilateral germ cell tumors but rare in those with unilateral disease (Rajpert-De Meyts, 2006) This finding suggests that mutations had occurred prior to migration of primordial germ cells early in life and patients with c-kit mutations are prone to develop bilateral germ cell tumors Recently, OCT3/4 has become one of the most widely used germ cell tumor markers due to its high specificity... testicular germ cell tumors: Twenty-five year experience in Munich." Acta Oncol 44(6): 529-536 Hoei-Hansen, C E., Almstrup, K., Nielsen, J E., Brask Sonne, S., Graem, N., Skakkebaek, N E., Leffers, H & Rajpert-De Meyts, E (2005a) "Stem cell pluripotency factor NANOG is expressed in human fetal gonocytes, testicular carcinoma in situ and germ cell tumours." Histopathology 47(1): 48-56 Intratubular Germ Cell. .. non-seminomatous germ cell tumor of the testis 1.1.1 Introduction to clinical stage I disease About 5-7/100,000 men are diagnosed with testis cancer annually A large proportion of these are pathologically classified as non-seminomatous germ cell tumor (NSGCT) The majority of NSGCT patients present with clinical stage (CS) I disease, which is characterized by a germ cell tumor confined to the testis,... & Skakkebaek, N E (1988a) "A monoclonal antibody as a marker for carcinoma in situ germ cells of the human adult testis." APMIS 96(8): 667-670 Giwercman, A., Marks, A & Skakkebaek, N E (1988b) "Carcinoma-in-situ germ- cells exfoliated from seminiferous epithelium into seminal fluid." Lancet 1(8584): 530 18 Germ Cell Tumor Giwercman, A., Muller, J & Skakkebaek, N E (1991a) "Prevalence of carcinoma in... including this review, is intratubular germ cell neoplasia, unclassified (ITGCN) ITCGN plays an important role in the development of TGCTs Since the seminal work by Skakkebaek, it has been generally accepted that most TGCTs arise from ITGCN, with the notable exception of pediatric germ cell tumors (yolk sac, mature teratoma) and the rare spermatocytic seminomas Subsequent work by von der Maase et al demonstrated... and germ cell tumors." Clin Cancer Res 10(24): 8521-8530 Hoei-Hansen, C E., Rajpert-De Meyts, E., Daugaard, G & Skakkebaek, N E (2005b) "Carcinoma in situ testis, the progenitor of testicular germ cell tumours: a clinical review." Ann Oncol 16(6): 863-868 Holm, M., Hoei-Hansen, C E., Rajpert-De Meyts, E & Skakkebaek, N E (2003) "Increased risk of carcinoma in situ in patients with testicular germ cell. .. electron microscopical analysis of cell types in human seminoma." Virchows Arch A Pathol Anat Histol 363(2): 97-112 Holstein, A F & Lauke, H (1996) "Histologic diagnostics of early testicular germ- cell tumor. " Int J Urol 3(3): 165-172 Holzbeierlein, J M., Sogani, P C & Sheinfeld, J (2003) "Histology and clinical outcomes in patients with bilateral testicular germ cell tumors: the Memorial Sloan Kettering... carcinoma in situ of the testis also expressed in normal infantile germ cells." Histopathology 22(4): 373-378 20 Germ Cell Tumor Kleinschmidt, K., Dieckmann, K P., Georgiew, A., Loy, V & Weissbach, L (2009) "Chemotherapy is of limited efficacy in the control of contralateral testicular intraepithelial neoplasia in patients with testicular germ cell cancer." Oncology 77(1): 33-39 Kliesch, S., Thomaidis, T.,... "Chromosomal imbalances associated with carcinoma in situ and associated testicular germ cell tumours of adolescents and adults." Br J Cancer 85(2): 213-220 Tan, I B., Ang, K K., Ching, B C., Mohan, C., Toh, C K & Tan, M H (2010) "Testicular microlithiasis predicts concurrent testicular germ cell tumors and intratubular germ cell neoplasia of unclassified type in adults: a meta-analysis and systematic review."... testicular germ cell cancer among infertile men." Arch Intern Med 169(4): 351-356 Wood, H M & Elder, J S (2009) "Cryptorchidism and testicular cancer: separating fact from fiction." J Urol 181(2): 452-461 2 Management of Nonseminomatous Germ Cell Tumor of the Testis Paul H Johnston and Stephen D.W Beck Indiana University, USA 1 Introduction 1.1 Management options for clinical stage I non-seminomatous germ cell . GERM CELL TUMOR Edited by Angabin Matin Germ Cell Tumor Edited by Angabin Matin Published by InTech Janeza. common type of germ cell tumors of the testes, non-seminomatous germ cell tumors. In Chapter 3, Takamitsu Fujimaki reviews intracranial germ cell tumors, which