Abstract
Abstract Introduction. 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 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. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4562. doi:1538-7445.AM2012-4562
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