Caveolin-1 overexpression is associated with aggressive prostate cancer recurrence

BACKGROUND. Caveolin-l protein suppresses apoptotic cell death in prostate cancer. The objectives of this study were to investigate the association of Caveolin-1 expression with established features of prostate cancer as well as overall and aggressive disease recurrence in patients treated with radical prostatectomy (RP). METHODS. Caveolin-1 immunostaining was performed on a tissue microarray containing prostatectomy specimen cores from 232 consecutive patients treated with RP for clinically localized prostatic adenocarcinoma. Caveolin-1 over-expression was defined as more than 50% of cells staining positively for Caveolin-1. Patients were categorized as having features of aggressive disease recurrence if they had a positive metastatic work-up, post-recurrence PSA doubling time less than 10 months, and/or failure to respond to local salvage radiation therapy. RESULTS. Seventy patients (30.2%) exhibited over-expression of Caveolin-1. Caveolin-1 overexpression was associated with higher pathologic Gleason sum (P = 0.038) and higher preoperative PSA level (P = 0.024). Patients with Caveolin-1 over-expression were at increased risk of PSA recurrence after surgery (P = 0.023) in univariate but not in standard post-operative multivariate analysis. However, patients with Caveolin-l over-expression were at increased risk of aggressive prostate cancer recurrence in both univariate and multivariate analysis (P < 0.001 and P = 0.001, respectively). CONCLUSIONS. Over-expression of Caveolin-1 was associated with established features of prostate cancer and aggressive PSA recurrence. Caveolin-1 might help identify patients at high risk of developing aggressive prostate cancer recurrence, thus allowing selection of patients who might benefit from early systemic therapeutic intervention.