Abstract 1172:RARBis a biomarker of poor prognosis in prostate carcinomas

Abstract Purpose: Despite the advances in prostate carcinomas (PCa) management, about 30% of the patients who undergo radical prostatectomy presented biochemical recurrence (BCR). BCR is considered an unfavorable prognostic factor followed by clinical disease progression. The current prognostic markers in PCa are unable detect correctly who is at risk for BCR. Hypermethylation at RARB and RASSF1A genes have been associated with worse prognosis in PCa. The current study aimed to evaluate RARB, and RASSF1A hypermethylation frequencies in prostate carcinoma (PCa) and to correlate these alterations with down-regulation at transcriptional and protein levels and with clinical outcome. Methods: Methylation patterns of RARB and RASSF1A were determined by methylation-specific PCR in 68 PCa samples and 27 non-neoplastic prostate tissues. Gene expression was evaluated by quantitative RT-PCR in 73 PCa, 15 adjacent non-neoplastic prostate tissues (AdjP) and two normal prostate (N). Protein expression was evaluated in an independent PCa cohort (n=141) with long-term follow-up period. The findings were associated with clinicopathological parameters and BCR-free survival (BRFS). Results: RARB and RASSF1A genes were hypermethylated in PCa (P <0.0001 and P = 0.0017, respectively). RASSF1A mRNA and protein levels were similar in PCa and AdjP samples. Down-expression of RARβ in transcript (P=0.001) and protein (P=0.0007) levels were detected in PCa. Lower mRNA levels were associated with RARB hypermethylation. Nuclear and cytoplasmic RARβ protein expression was detected in tumor tissues. Multivariate analysis demonstrated that cytoplasmic RARβ immunostaining was independently associated with decreased BRFS (P=0.005, HR=2.314). Conclusions: RARB hypermethylation seems to be one of the mechanisms involved in RARβ down-expression in PCa. Cytoplasmic RARβ protein is an independent predictor of poor prognosis that may be considered a new biomarker in prostate cancer providing, therefore, relevant information for patient management. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1172.