920 EXPRESSION OF HISTONE DEACETYLASES 1,2 AND 3 IN UROTHELIAL BLADDER CANCER

Abstract

You have accessJournal of UrologyBladder Cancer: Basic Research (II)1 Apr 2013920 EXPRESSION OF HISTONE DEACETYLASES 1,2 AND 3 IN UROTHELIAL BLADDER CANCER Cédric Poyet, Bastian Jentsch, Thomas Hermanns, Peter Wild, Martin Schmidtpeter, Daniel Schweckendieck, Tullio Sulser, Holger Moch, and Glen Kristiansen Cédric PoyetCédric Poyet Zürich, Switzerland More articles by this author , Bastian JentschBastian Jentsch Zürich, Switzerland More articles by this author , Thomas HermannsThomas Hermanns Zürich, Switzerland More articles by this author , Peter WildPeter Wild Zürich, Switzerland More articles by this author , Martin SchmidtpeterMartin Schmidtpeter Zürich, Switzerland More articles by this author , Daniel SchweckendieckDaniel Schweckendieck Zürich, Switzerland More articles by this author , Tullio SulserTullio Sulser Zürich, Switzerland More articles by this author , Holger MochHolger Moch Zürich, Switzerland More articles by this author , and Glen KristiansenGlen Kristiansen Zürich, Switzerland More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.497AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Superficial urothelial bladder cancer recurs in around 70 % after transurethral resection and 10-20 % of them show progression into muscle-invasive bladder cancer (MIBC). Due to the worse prognosis of MIBC, there is a high interest in identifying markers that can diagnose superficial cancers with a high risk of progression. Histone deacetylases (HDACs) are involved in different cellbiological processes like proliferation and differentiation and are known to be overexpressed in some cancer tumors. A range of much more potent, structurally diverse HDAC inhibitors can inhibit tumor growth and have been already clinically validated in cancer patients with hematologic malignancies. According to the literature only few data for HDAC expression in urothelial cancer is available. Ki-67 overexpression in urothelial cancer and its association with worse prognosis has been shown in several studies. METHODS In this study we aimed to evaluate the protein expression of class I histone deacetylases (HDAC) in urothelial bladder cancer. 189 primary urothelial bladder cancer were included in a tissue microarray. Median follow-up of the cohort was 6.7 years (3 to 36 years). The final TMA contents 105 pTa tumors, 71 pT1 and 13 pT2 or higher. Expression of class I HDAC isoforms 1, 2 and 3 and Ki67 was assessed by immunohistochemistry. To study statistical associations between clinicopathologic and immunohistochemical data chi-Square test and Spearman-correlation were used. Progression free survival curves were calculated using the KaplanûMeier method with significance evaluated by 2-sided log-rank statistics. P < 0.05 was considered significant. RESULTS A significant association of Ki67 expression was found with t-stage, grading and progression free survival. This reveals the comparability to other constructed urothelial TMAs. HDAC were highly expressed in about 40 to 60 % of all cases (HDAC-1 40 %, HDAC-2 44 %, HDAC-3 59 %). Furthermore we observed a significant overexpression of HDAC-2 in higher staged or higher graded tumors. However, there was no significant association with progression free survival. CONCLUSIONS HDAC-2 was associated with more aggressive pathological parameters like t-stage and grading. In contrary to Ki67, a relevant prognostic value for HDAC 1-3 could not be demonstrated. However, the high expression levels of HDACs in urothelial bladder cancer might still be indicative for a treatment response to HDAC inhibitors which ought to be evaluated in further studies. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e378 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Cédric Poyet Zürich, Switzerland More articles by this author Bastian Jentsch Zürich, Switzerland More articles by this author Thomas Hermanns Zürich, Switzerland More articles by this author Peter Wild Zürich, Switzerland More articles by this author Martin Schmidtpeter Zürich, Switzerland More articles by this author Daniel Schweckendieck Zürich, Switzerland More articles by this author Tullio Sulser Zürich, Switzerland More articles by this author Holger Moch Zürich, Switzerland More articles by this author Glen Kristiansen Zürich, Switzerland More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...