High level of androgen receptor is associated with aggressive clinicopathologic features and decreased biochemical recurrence-free survival in prostate - Cancer patients treated with radical prostatectomy

Background: Prostate cancer (PCa) is androgen dependent and is regulated by androgen/androgen receptor (AR) signaling pathway. However, the clinical significance of AR is in question. In this regard, we have correlated levels of AR expression with some well-established clinical and pathologic parameters and assessed the prognostic value of AR expression in PCa patients treated with radical prostatectomy. Design: A total of 640 cases treated with radical prostatectomy were used to build tissue microarrays. Normal prostate tissue, benign prostatic hyperplasia, and index tumor were cored in triplicate (0.6 mm). An array (2 mm) of 177 metastatic PCa was built as well. Slides were immunostained with an antibody to AR and Ki-67 and digitized. Correlations between AR expression and clinicopathologic variables were analyzed by the Spearman test. Biochemical recurrence-free survival analysis was performed using Kaplan-Meier analysis, and Cox proportional hazard regression was used to determine the probability of disease recurrence. Results: AR was found in epithelial nuclei of both benign and cancer tissues. AR index was higher in normal prostate tissues than that in PCa and benign prostatic hyperplasia and decreased in metastases than PCa. High level of AR expression was correlated with clinical stage, lymph node status, extracapsular extension, seminal vesicle invasion, and Gleason score. High levels of AR status also correlated with high Ki-67 index (r(2) = 0.211, P = 0.0000). By Kaplan-Meier actuarial model, high expression of AR was predictive of a higher probability of recurrence (P = 0.0046, hazards ratio 2.72 [confidence interval 1.28-4.011]). By multivariate analysis, a high level of AR expression was an independent prognostic indicator of biochemical recurrence-free survival (P = 0.0042; hazards ratio 2.422 [confidence interval 1.32-4.44]). Conclusions: High levels of AR are associated with increased proliferation, markers of aggressive disease and are predictive of decreased biochemical recurrence-free survival independently. This confirms the role of AR in tumor growth and progression in hormonally naive PCa.