Abstract 3809: TMPRSS2-ERG gene fusion is strongly associated with elevated androgen receptor expression in early prostate cancer

Abstract

Abstract Introduction and Objective: About 50% of prostate cancers have TMPRSS2-ERG fusions resulting in ERG overexpression. The aim of this study was to determine whether prostate cancer of “fusion-type” differs from “non-fusion” prostate cancer both clinically and molecularly. Methods: A prostate cancer tissue microarray (TMA) consisting of over 2,500 cancer samples was analyzed for ERG protein expression and TMPRSS2-ERG gene fusion by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Results were compared with tumor phenotype, clinical outcome, and molecular features previously determined in studies using the same TMA. Furthermore, a fresh frozen prostate cancer TMA containing 41 “fusion-type” and 21 “non-fusion” prostate cancers was analyzed by MALDI (Matrix Assisted Laser Desorption/Ionisation) mass spectrometric imaging, a technology analyzing proteomic patterns directly on tissue sections. Functional analyses included comparisons of androgen receptor (AR) mRNA levels in LNCaP cells before and after induced ectopic ERG overexpression through lentiviral vectors. Results: Detectable ERG protein expression was found in 52% of 2818 interpretable cancers on our TMA and TMPRSS2-ERG fusion was observed by FISH in 42% of 947 interpretable cases. The data did not reveal any clinical or prognostic significance of ERG protein expression and TMPRSS2-ERG fusion. However, several molecular features differed between “”fusion-type” and “non-fusion” prostate cancers, including AR, AMACR, Annexin A3, Bcl2, CD10, CD166, Chromogranin A, EGFR, HER2 and mTOR. The strongest difference was found for AR expression, which was considered strong in 62.9% of ERG negative but in 81.0% of ERG positive cancers. In the LNCaP cell line, ectopic ERG overexpression lead to a marked downregulation of androgen receptor dependent transcription. MALDI imaging identified several additional masses that differed significantly between “fusion-type” and “non-fusion” tumors. Conclusions: There is no particular clinical behavior of “fusion-type” and “non-fusion” cancers in surgically treated patients. The TMPRSS2-ERG fusion determines a distinct subgroup of prostate cancers, which strongly differ on the molecular level as detected by immunohistochemistry and MALDI imaging. Furthermore, our data indicate that ERG modulates the transcription of AR-dependent genes in prostate cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3809. doi:10.1158/1538-7445.AM2011-3809