CANCER OF THE UTERINE ENDOMETRIUM – ADVANCES AND CONTROVERSIES Edited by J. Salvador Saldivar           Cancer of the Uterine Endometrium – Advances and Controversies Edited by J. Salvador Saldivar 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 Iva Simcic Technical Editor Teodora Smiljanic Cover Designer InTech Design Team First published February, 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@intechweb.org Cancer of the Uterine Endometrium – Advances and Controversies, Edited by J. Salvador Saldivar p. cm. ISBN 978-953-51-0142-0   Contents  Preface IX Part 1 Biology and Genetics 1 Chapter 1 Molecular Biology of Endometrial Carcinoma 3 Ivana Markova and Martin Prochazka Chapter 2 The Role of ErbB Receptors in Endometrial Cancer 23 Adonakis Georgios and Androutsopoulos Georgios Chapter 3 Hereditary Endometrial Carcinoma 39 J. Salvador Saldivar Part 2 Modern Imaging and Radiotherapy 55 Chapter 4 Diagnostic Value of Dynamic Contrast-Enhanced MRI in Endometrial Cancer 57 Ting Zhang, Ai-Lian Liu, Mei-Yu Sun, Ping Pan, Jin-Zi Xing and Qing-Wei Song Chapter 5 Modern External Beam Radiotherapy Techniques for Endometrial Cancer 77 Ruijie Yang and Junjie Wang Part 3 Surgery and Staging 85 Chapter 6 Controversies in the Surgery of Endometrial Cancer 87 F. Odicino, G.C. Tisi, R. Miscioscia and B. Pasinetti Chapter 7 Controversies Regarding the Utility of Lymphadenectomy in Endometrial Cancer 101 Frederik Peeters and Lucy Gilbert VI Contents Part 4 Therapeutic Strategies 121 Chapter 8 Treatment Strategies and Prognosis of Endometrial Cancer 123 Gunjal Garg and David G. Mutch Chapter 9 Reducing the Risk of Endometrial Cancer in Patients Receiving Selective Estrogen Receptor Modulator (SERM) Therapy 149 Victor G. Vogel Chapter 10 Adjuvant Chemotherapy for Endometrial Cancer 167 N. Susumu, H. Nomura, W. Yamagami, A. Hirasawa, K. Banno, H. Tsuda, S. Sagae and D. Aoki   Preface  Cancer of the uterine endometrium is the most common gynecological cancer in developed countries, and the most common gynecologic cancer in the USA. Obesity, diabetes and a hyper-estrogen state are common risk factors associated with the majority of uterine cancer cases. Although most women with endometrial cancer are diagnosed at an early stage, it is still a significant cause of gynecologic cancer-related morbidity and mortality. The primary treatment of endometrial cancer is surgical, however, there still remains controversy regarding the survival benefit following complete lymphadenectomy. Further, the roles of combination chemotherapeutic agents, radiotherapy techniques and hormonal treatment are continually evolving. This first edition of Cancer of the Uterine Endometrium - Advances and Controversies brings together an international collaboration of authors to attempt to address these issues. Effective treatment of any gynecologic cancer is best approached via a multidisciplinary model that includes physicians, scientists and oncologic personnel, among others, to improve the outcome for women. The book is divided into four sections in an attempt to emulate this multi-faceted model of collaboration: 1) Biology and Genetics, including hereditary endometrial cancer; 2) Modern Imaging and Radiotherapy; 3) Surgery and Staging; and 4) Therapeutic Strategies. Each section brings forth the most relevant and evidence-based information for the diagnosis and treatment of endometrial cancer. In addition, controversies regarding therapeutic strategies are addressed in the context of the latest clinical studies. This book is not intended to cover the basics of endometrial cancer. For this, one should refer to a number of excellent gynecologic oncology textbooks. Rather, the vision of this book is an international expert collaboration of the most updated advances in the biology, genetics, diagnosis, imaging, and treatment strategies for cancer of the uterine endometrium. Ultimately, it is hoped that this opens a platform for which other authors may add their work in future editions of this book. It is meant for all learners who care for women with this gynecologic cancer. It is dedicated to our women patients, our best teachers.  Asst. Prof. Dr. J. S. Saldivar MD, MPH Division of Gynecology Oncology, TTUHSC-El Paso, Texas USA [...]... of the cycle is mostly under the influence of oestrogens that stimulate proliferation of epithelial and stromal endometrial components, whereas during the secretory stage the main function 16 Cancer of the Uterine Endometrium – Advances and Controversies of progesterone is glandular differentiation and glycogenesis with inhibition of oestrogenmediated proliferation Just as the ovarian steroids play an... epigenetic and proteomic changes The application of molecular biology techniques, including analysis of methylation and acetylation, and preoteomic techniques have become an important tool not only in basic research but also when determining the appropriate therapy 18 Cancer of the Uterine Endometrium – Advances and Controversies The significance of various immunohistochemical parameters for the prognosis... PMS1 and PMS2 ) among the tumour suppressor genes The vast majority of patients 12 Cancer of the Uterine Endometrium – Advances and Controversies carry so called Lynch syndrome, also known as HNPCC (hereditary nonpolyposis colorectal cancer) HNPCC is a familial cancer syndrome caused by mutations in one of five different genes for DNA repair responsible for the repair of DNA segments in which the correct... various types of repetitive sequences, i.e DNA sections of various length that appear in many copies at various places of the genome Most of them are products of reverse transcription and thus they have a crucial effect on the structure of the genome in Molecular Biology of Endometrial Carcinoma 13 humans and other organisms The importance of the repetitive sequences probably lies in maintaining the chromosomal... loss of function in both alleles of a certain gene, are identified as tumour suppressor genes They regulate cell division or are involved in contact inhibition of cell growth - they function as "safety fuses" which turn off the cell cycle if exposed to 8 Cancer of the Uterine Endometrium – Advances and Controversies abnormal proliferation or damage to genetic information Their protein products check the. .. domain and an intracellular domain with tyrosine kinase activity [Riese et al., 2007; Yarden, 2001a; Yarden & Sliwkowski, 2001b] They catalyze the transfer of the γ phosphate of ATP to hydroxyl groups of tyrosines in target proteins [Hunter, 1998] ErbB-3 lacks intrinsic tyrosine kinase activity [Mass, 2004] 24 Cancer of the Uterine Endometrium – Advances and Controversies The extracellular region of ErbB... demonstrate the correlation between an abnormally increased expression of p53 and aggressive histological types, advanced stage 10 Cancer of the Uterine Endometrium – Advances and Controversies of disease and shorter survival time (Cherchi et al., 2001, Marková et al., 2010, Ohkouchi et al., 2002) It seems that the p53 gene mutations play an important role primarily in the late stages of endometrial... during the excessive and mostly chaotic and imprecise division, other changes are cumulated and new characteristics acquired Therefore, the metastatic cells do not reveal different genetic changes than the cells of the original tumour However, all these cells emerged through the division of a single originally maligned cell and thus the tumour is termed as monoclonal The above indicates that the complex... damaged DNA The original clone of neoplastic 4 Cancer of the Uterine Endometrium – Advances and Controversies cells may, in this way, develop into many sublines with a different degree of malignity Thus, the cell clone able to survive is selected, i.e clonal selection Such tumorous cells generally acquire the ability of invasive growth and metastases Each malignant tumour is a mixture of cells with... and is associated with negative prognostic factors, such as advanced stage of disease and lower degree of histological differentiation (Mariani et al., 2003) It is highly probable that the increased expression of this oncogene might be 6 Cancer of the Uterine Endometrium – Advances and Controversies among the late events in the endometrial carcinoma carcinogenesis, whereas in serous carcinoma it concerns . CANCER OF THE UTERINE ENDOMETRIUM – ADVANCES AND CONTROVERSIES Edited by J. Salvador Saldivar           Cancer of the Uterine Endometrium – Advances and Controversies. Further, the roles of combination chemotherapeutic agents, radiotherapy techniques and hormonal treatment are continually evolving. This first edition of Cancer of the Uterine Endometrium - Advances. demonstrate the correlation between an abnormally increased expression of p53 and aggressive histological types, advanced stage Cancer of the Uterine Endometrium – Advances and Controversies 10 of