Abstract 2124: Comprehensive analysis of hormone receptor status during prostate cancer progression: A novel prognostic role for pAR and ERbeta

Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL Aims: Patients with advanced prostate cancer (PrCa) are usually treated with androgen withdrawal. Although this therapy is effective at the beginning, nearly all prostate cancers become refractory to it. Hormone receptors play a crucial role during this progression. Aim of this study was to analyze the genomic and expression status of hormone receptors in prostate cancer and the evolution of these markers in the development of castration-resistance. Methods: We selected 915 transurethral resection (TURP) specimens from 107 untreated PrCa and from 101 castration-resistant (CR) PrCa. These samples were used for the construction of a tissue microarray (TMA). In addition, we included 56 distant metastases. We analyzed the androgen receptor (AR) gene copy number by fluorescence in-situ hybridization and the expression profiles of AR, phosphorylated AR (pAR), ERβ, ERα and the proliferation marker Ki67 by immunohistochemistry. Results: AR gene amplification was almost restricted to PrCa and was significantly associated with increased AR protein expression (p<0.0001) and higher tumor cell proliferation (p=0.001). Interestingly, although pAR was predominantly found in the CR PrCa (p=0.003), pAR expression in untreated PrCa patients identified a subgroup of patients with poor survival (p<0.05). In contrast to ERα expression, which was restricted to CR PrCA cells (10%), ERβ was found in 40% of the PrCa, independent of treatment status. Similar to pAR, the presence of ERβ in untreated patients was significantly associated with adverse prognosis (p<0.005). Conclusions: This is the first comprehensive study comparing the hormonal receptor status in a large cohort of hormone-naive and CR PrCa. Our results strongly suggest a major role for pAR and ERβ in untreated PrCa. Expression of these markers might be a mechanism of CR tumor growth. 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 2124. doi:10.1158/1538-7445.AM2011-2124