319 COMPREHENSIVE ANALYSIS OF THE TMPRSS2-ERG TRANSLOCATION DURING PROSTATE CANCER PROGRESSION
2012-04-01

You have accessJournal of UrologyProstate Cancer: Basic Research II1 Apr 2012319 COMPREHENSIVE ANALYSIS OF THE TMPRSS2-ERG TRANSLOCATION DURING PROSTATE CANCER PROGRESSION Shyh-Han Tan, Christian Ruiz, Martin Braun, Veit Scheble, T. Zellweger, C.A. Rentsch, A. Bachmann, Albert Dobi, Sven Perner, Isabell Sesterhenn, Shiv Srivastava, and L. Bubendorf Shyh-Han TanShyh-Han Tan Rockville, MD More articles by this author , Christian RuizChristian Ruiz Basel, Switzerland More articles by this author , Martin BraunMartin Braun Bonn, Germany More articles by this author , Veit SchebleVeit Scheble Tuebingen, Germany More articles by this author , T. ZellwegerT. Zellweger St. Claraspital, Switzerland More articles by this author , C.A. RentschC.A. Rentsch Basel, Switzerland More articles by this author , A. BachmannA. Bachmann Basel, Switzerland More articles by this author , Albert DobiAlbert Dobi Rockville, MD More articles by this author , Sven PernerSven Perner Bonn, Germany More articles by this author , Isabell SesterhennIsabell Sesterhenn Rockville, MD More articles by this author , Shiv SrivastavaShiv Srivastava Rockville, MD More articles by this author , and L. BubendorfL. Bubendorf Basel, Switzerland More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.379AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Approximately half of the diagnosed prostate carcinomas (PC) are characterized by a chromosomal rearrangement fusing the androgen regulated gene TMPRSS2 to the oncogenic ETS transcription factor ERG. Aim of this study was to comprehensively analyze the impact of this translocation on the expression of the ERG gene in hormone-naïve (untreated) and castration-resistant prostate cancers and to define the influence of AR protein expression and genomic amplification in this context. METHODS We constructed a tissue microarray (TMA) containing 915 tissue cores from 107 hormone-naïve PC and from 101 castration-resistant (CR) PC. In addition, we included 56 specimens from distant metastases. We analyzed the TMPRSS2-ERG translocation status by fluorescence in-situ hybridization and the expression profiles of ERG, AR and the proliferation marker Ki67 by immunohistochemistry. RESULTS Nearly half of the analyzed PC tissue specimens (untreated: 38%, castration-resistant: 46%) harbored a TMPRSS2-ERG gene fusion. Untreated PC with positive translocation status showed increased tumor cell proliferation (p<0.05). As expected, TMPRSS2-ERG gene fusion was strongly associated with increased ERG protein expression in untreated, as well as in castration-resistant PC (both p<0.0001). However, we detected a subgroup (26%) of CR PCs with the gene fusion, but without detectable ERG protein expression. This subgroup showed significantly lower levels of AR protein expression and of the androgen regulated serum PSA (both p<0.05). CONCLUSIONS This comprehensive study comparing the TMPRSS2-ERG gene and ERG protein expression status in a large cohort of hormone-naïve and CR PC, identifies a subgroup of translocated CR PCs without ERG protein expression. Our results suggest that this subgroup may represent CR PCs with a dispensed AR pathway. Further analyses may help to explain if these tumors represent a distinct subgroup of AR independent CR PCs. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e129 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Shyh-Han Tan Rockville, MD More articles by this author Christian Ruiz Basel, Switzerland More articles by this author Martin Braun Bonn, Germany More articles by this author Veit Scheble Tuebingen, Germany More articles by this author T. Zellweger St. Claraspital, Switzerland More articles by this author C.A. Rentsch Basel, Switzerland More articles by this author A. Bachmann Basel, Switzerland More articles by this author Albert Dobi Rockville, MD More articles by this author Sven Perner Bonn, Germany More articles by this author Isabell Sesterhenn Rockville, MD More articles by this author Shiv Srivastava Rockville, MD More articles by this author L. Bubendorf Basel, Switzerland More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...