214 IDENTIFICATION OF CHARACTERISTIC GENE EXPRESSION IN SARCOMATOID RENAL CELL CARCINOMA

Abstract

You have accessJournal of UrologyKidney Cancer: Basic Research II1 Apr 2010214 IDENTIFICATION OF CHARACTERISTIC GENE EXPRESSION IN SARCOMATOID RENAL CELL CARCINOMA Takahiro Kojima, Toru Shimazui, Takehiro Oikawa, Koji Kawai, Kazuhiko Uchida, and Hideyuki Akaza Takahiro KojimaTakahiro Kojima More articles by this author , Toru ShimazuiToru Shimazui More articles by this author , Takehiro OikawaTakehiro Oikawa More articles by this author , Koji KawaiKoji Kawai More articles by this author , Kazuhiko UchidaKazuhiko Uchida More articles by this author , and Hideyuki AkazaHideyuki Akaza More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.271AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Sarcomatoid renal cell carcinoma is characterized by most aggressive phenotype in renal cell carcinoma (RCC). Currently, sarcomatoid RCC could derive from all subtype of RCC, including clear cell, papillary, chromophobe, and collecting duct carcinoma. Sarcomatoid RCC is highly resistant to therapeutics including conventional cytokine therapy and targeted therapeutics such as sorafenib and sunitinib. Because little is known about the molecular mechanisms of sarcomatoid differentiation and transformation, we have performed microarray analyses to identify characteristic gene expression for sarcomatoid RCC. METHODS We analyzed gene expression profiles in surgical specimens of clear-cell derived sarcomatoid RCC (n=2), clear-cell RCC (n=12) and corresponding normal kidney (n=12) using GeneChip (Human Genome U133 Plus 2.0 array, Affymetrix). Differentially expressed genes between sarcomatoid and clear-cell RCC were determined (ANOVA p=0.01, at least 5-fold change). Microvessel density (MVD) was examined by CD34 immunohistochemistry. RESULTS We identified 207 up-regulated and 545 down-regulated genes in sarcomatoid RCC compared to clear-cell RCC. Among them, ZFHX1B, CDH1, CTNNA1 and OCLN were specifically expressed in sarcomatoid RCC. MAFB transcription factor associated with hematopoiesis and ETV5 transcription factor were significantly up-regulated in sarcomatoid RCC. KLF6, KL and NDRG2, potential tumor suppressors, were significantly down-regulated in sarcomatoid RCC. VEGF was up-regulated in clear-cell RCC but not in sarcomatoid RCC and MVD in sarcomatoid component is lower than that in clear-cell component. CONCLUSIONS These results suggest that epithelial-mesenchymal-transition is an important process in sarcomatoid development and VEGF-targeted therapy might be less effective in sarcomatoid RCC. Further investigations lead us to identify molecular target in development of targeted therapeutics for sarcomatoid RCC. Tsukuba, Japan© 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e84 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Takahiro Kojima More articles by this author Toru Shimazui More articles by this author Takehiro Oikawa More articles by this author Koji Kawai More articles by this author Kazuhiko Uchida More articles by this author Hideyuki Akaza More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...