RENAL TUMOR Edited by Jindong Chen Renal Tumor http://dx.doi.org/10.5772/56083 Edited by Jindong Chen Contributors Tetsuo Fujita, Masatsugu Iwamura, Kazumasa Matsumoto, Kazunari Yoshida, Mirjana Rajer, Carolin Eva Hach, Stefan Siemer, Stephan Buse, Akihiro Tojo, Luis Miguel Anton Aparicio, Luis Leon, Martin Lazaro, Javier Afonso, Sergio Vazquez Estevez, Urbano Anido, Ovidio Fernandez, Manuel Ramos, María Carmen Areses Manrique, Henryk Zielinski, Tomasz Syrylo, Stanislaw Szmigielski, Archil Chkhotua, Ryoiti Kiyama, Vasiliki Michalaki, Sina Vatandoust, Thean Hsiang Tan, Michail Charakidis Published by InTech Janeza Trdine 9, 51000 Rijeka, Croatia Copyright © 2013 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. 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 Viktorija Zgela Technical Editor InTech DTP team Cover InTech Design team First published February, 2013 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 Renal Tumor, Edited by Jindong Chen p. cm. ISBN 978-953-51-0981-5 free online editions of InTech Books and Journals can be found at www.intechopen.com Contents Preface VII Section 1 Molecular Biology of Renal Tumor 1 Chapter 1 Genetics of Renal Tumors 3 Ryoiti Kiyama, Yun Zhu and Tei-ichiro Aoyagi Chapter 2 Signaling Pathways and Biomarkers in Renal Tumors 31 Tetsuo Fujita, Masatsugu Iwamura, Kazumasa Matsumoto and Kazunari Yoshida Chapter 3 Imagen Thecniques in Renal-Cell Carcinoma 45 L. León, M. Ramos, M. Lázaro, S. Vázquez, M. C. Areses, O. Fernandez, U. Anido, J. Afonso and L. A. Aparicio Section 2 Management of Localized Renal Tumor 69 Chapter 4 Renal Cell Carcinoma: Clinical Surgery 71 Carolin Eva Hach, Stefan Siemer and Stephan Buse Chapter 5 Nephron-Sparing Surgery for the Treatment of Renal Cell Carcinoma 4 to 7 cm in Size 87 Ambrosi Pertia, Laurent Managadze and Archil Chkhotua Chapter 6 Renal Artery Embolization in Treatment of Renal Cancer with Emphasis on Response of Immune System 95 H. Zielinski, T. Syrylo and S. Szmigielski Chapter 7 Paraneoplastic Glomerulopathy Associated with Renal Cell Carcinoma 109 Akihiro Tojo Section 3 Management of Metastatic/Advanced Renal Tumor 131 Chapter 8 Surgical and Oncological Results of Treatment of Metastases of Renal Cell Carcinoma to the Contralateral Adrenal Gland 133 Archil Chkhotua, Laurent Managadze and Ambrosi Pertia Chapter 9 Current Perspectives in Metastatic Renal Cell Carcinoma Treatment: The Role of Targeted Therapies 145 V. Michalaki, M. Balafouta, D. Voros and C. Gennatas Chapter 10 New Systemic Treatment Approaches for Metastatic Renal Cell Carcinoma 157 Thean Hsiang Tan, Sina Vatandoust and Michail Charakidis Chapter 11 Changing Mechanisms of Action as a Strategy for Sequential Targeted Therapy of Metastatic Renal-Cell Carcinoma 187 Mirjana Rajer ContentsVI Preface Renal cell carcinoma (RCC) is the most common type (>80%) of kidney cancer that arises from the cells of the renal tubules. Although RCC is relatively rare and only represents approximately 3% of all adult cancer, an alarming increase in incidence has been observed in the past five decades. Worldwide, approximately 150,000 new cases are diagnosed with RCC each year, and around 95,000 affected people die from the disease annually. While patients with early, localized RCC have a good prognosis, those with advanced disease (metastatic RCC) do not respond to most traditional therapeutic approaches, and survival for such patients is often less than 1 year. Unfortunately, most patients are diagnosed with advanced RCC, which causes anti-RCC treatment more challenging. Even so, with the advent and improvement of edge-cutting biomedical techniques, a significant amount of new information concerning the epidemiology, molecular genetics, immunologic char‐ acteristics, and therapy for patients with these tumors has appeared. Through the integration of molecular-based technologies, systematic tissue procurement and medical informatics, research data can rapidly be translated into useful diagnostic and treatment strategies. In fact, the increasing understanding of the pathogenesis of RCC has led to the development of novel targeted agents. New anti-RCC drugs have now been approved and commercially available, some potential drugs are also under clinical trial. Here, to provide urologist and kidney cancer researchers with updated knowledge of RCC biolo‐ gy, current treatment practices, and novel treatment strategies, experts from all over the world, combining their our experience, explored and reviewed the latest developments in molecular ge‐ netics, surgery, and novel therapeutic strategies for renal tumors and organized into this book Renal Tumor. This book contains 11 chapters in three parts, covering the roles of partial nephrec‐ tomy, radical nephrectomy, and laparoscopy, as well as the latest developments in molecular ge‐ netics and immune dysfunction, signal transduction, and anti-RCC drugs associated with the diseases. Also discussed are imaging and screening for RCC, its diagnosis, paraneoplastic syn‐ dromes, and prognostic factors in metastatic disease. It is hoped that Renal Tumor will offer all physicians treating kidney cancer as well as researchers current practical knowledge about the nature, diagnosis, prognosis, management and treatment of this difficult disease. Finally, thanks to all the authors who have contributed their valuable time to write all the chap‐ ters. Without their efforts and dedication, the formation of this book would never be possible. Jindong Chen, Ph.D. Research Associate Professor, Co-director, Kidney Cancer Research Laboratory, Department of Urology University of Rochester Medical Center, Rochester, NY, USA Section 1 Molecular Biology of Renal Tumor [...]... therapeutics 3 Kank family genes and renal tumors 3.1 Structure of Kank-family genes The human Kank1 gene was found as a candidate tumor suppressor gene for renal tumors at 9p24, and encodes a protein containing ankyrin-repeats at the C-terminus and coiled-coil motifs near the N-terminus (Sakar et al., 2002) Based on domain and phylogenetic analyses, 11 12 Renal Tumor Kank2, Kank3 and Kank4 were found... mechanism is still not clear, Kank1 may block cytokinesis by regulating Rho activity through the interac‐ tion with Daam1 (Fig 3B) Therefore, it may reveal a new mechanism of regulation of cytokinesis and tumor suppression Genetics of Renal Tumors http://dx.doi.org/10.5772/54588 3.3 Kank-family genes and renal tumors The Kank1 gene was found at 9p24 by a comprehensive analysis of human chromosomes for... and chromophobe RCC, representing 80, 10, and 5% of all RCCs, and the majority of renal tumors are sporadic although 2-4% are hereditary (Hagenkord et al., 2011) A number of genes have been studied in association with renal tumors, including those involved in tumorigenesis, and the progression and outcome of the cancer, by means of mutational searches, gene expression profiling, proteomics/metabolomics... role in suppressing tumor development (Duns et al., 2012) NF2 was identified as a tumor suppressor gene by the analysis of knock-out mice (Mor‐ ris and McClatchey, 2009) The mice developed kidney tumors in 6-10 months with char‐ acteristics of hyperactive epidermal growth factor receptor (EGFR) signaling Merlin, the NF2 gene product, was implicated in suppressing tumorigenesis by inhibiting hyperacti‐... Monzon, F.A (2011) Clinical genomics of renal epithelial tumors Cancer Genet 204 (6), 285-297 Genetics of Renal Tumors http://dx.doi.org/10.5772/54588 [22] Hatano, N., Nishikawa, N.S., McElgunn, C., Sarkar, S., Ozawa, K., Shibanaka, Y., Nakajima, M., Gohiji, K., and Kiyama, R (2001) A comprehensive analysis of loss of heterozygosity caused by hemizygous deletions in renal cell carcinoma using a subtraction... decreased expression of Kank1 in high grade tumors (Zhu et al., 2011) Therefore, the Kank family genes may be related to renal carcinoma, and function as tumor suppressors A growth inhibitory effect of Kank1 has been reported Overexpression of Kank1 in HEK293 cells resulted in cell cycle arrest at G0/G1 On the other hand, growth suppres‐ sion of tumor cells was caused by Kank1 gene expression using nude mice... did not (Table 3) In clear cell RCC, 42% of grade 1 tumors were Kank1 negative, while 80% of grade 3 tumors were Kank1 positive In other histological types, there was no apparent difference among nuclear grades (most of them showed Kank1) When subdivided by pathological T stages, higher T stages of clear cell RCC showed a tendency to 17 18 Renal Tumor express Kank1 (p = 0.07) (Table 4) Other factors... less than ~10 Mb (Hatano et al., 2001; Sarkar et al., 2002; Fig 2) A tumor suppressor gene, Kank1, was found at 9p24 after extensive analysis of the LOH site by examining the loss of function upon its mutation; the loss of expression of the gene at mRNA and protein levels in RCC, and the loss of suppression of tumor growth in renal tumor cells (Sarkar et al., 2002) 2.4 Chromosomal abberations in RCC... regions in RCC LOH regions of less than ~10 Mb were identified as the minimum overlap‐ ping regions of LOH by subtraction cloning of mutated regions followed by the quantitative allelic analysis of over 60 RCC cases using microsatellite markers (see Hatano et al., 2001; Sarkar et al., 2002) 9 10 Renal Tumor Location LOH (%) 3p22-p23 15/16 (93.8) 3p21.2-p21.3 21/23 (91.3) 3q13.3-q21 13/31 (41.9) 5q12-q13.1... found in kidney tumors from BHD patients, suggesting this gene to be a tumor suppressor gene (Baldewijns et al., 2008) 2.1.6 Other genes Several genes were recently implicated in association with RCC, including BAP1, SETD2 and NF2, by means of advanced technologies such as the next-generation sequencing, a microarraybased analysis and a mouse transgene analysis BAP1 plays a role of a tumor suppressor . RENAL TUMOR Edited by Jindong Chen Renal Tumor http://dx.doi.org/10.5772/56083 Edited by Jindong Chen Contributors Tetsuo Fujita,. www.intechopen.com Additional hard copies can be obtained from orders@intechopen.com Renal Tumor, Edited by Jindong Chen p. cm. ISBN 978-953-51-0981-5 free online editions of InTech Books