Immunohistochemical Expression of Bcl2 is an Independent Predictor of Time-to-biochemical Failure in Patients with Clinically Localized Prostate Cancer Following Radical Prostatectomy

Abstract

Background: Whether the immunohistochemical expression (IHCE) of the bcl2, the p53 and of the prostate apoptosis response-4 (PAR4) proteins is associated with preoperative PSA levels, post-operative parameters of prostate cancer (PC) pathology, surgical staging or biochemical failure (BF) of patients with clinically localized PC who underwent radical prostatectomy (RP) of curative intent, was investigated. Patients and Methods: A retrospective analysis of clinical data evaluating surgical specimens of 131 patients with PC, consecutively treated with RP for clinically localized disease, was performed. The IHC method of streptavidin biotin peroxidase on paraffin tissue sections was used to detect bcl2 and p53 oncoproteins and PAR4 pro-apoptotic protein expression in surgical specimens. Results: Statistically significant relationships were detected between: (i) p53 IHC expression and infiltration of periprostatic tissue (IPT; p=0.011); (ii) tumor volume (TV; p=0.027); and (iii) bcl2 IHCE and absence of prostatic intraepithelial neoplasia (PIN) (p=0.004). Biochemical failure (BF) was documented in 37% of these patients. Kaplan-Meier survival curves showed that the IHCE of bcl2 and p53 was significantly related to BF. Taking the hazard ratio (HR) estimated from the Cox proportional hazard regression model to be 1.00 for patients with negative bcl2 IHCE, a value of 2.82 was found for patients with positive bcl2 IHCE (p=0.015, 95% CI=1.22-6.47). The HR for patients with positive p53 IHCE was 2.05 (p=0.048, 95% CI=1.00-4.19). Multivariate analysis showed that only seminal vesicle invasion (SVI), pelvic lymph node metastasis (PLNM) and bcl2 IHCE were independent predictors for BF (HR=3.06, 3.31 and 3.15; p=0.048, p=0.031 and p=0.031 for SVI, PLNM and bcl2 IHCE, respectively). Conclusion: Bcl2 immunohistochemical overexpression in specimens of RP suggests high risk for BF in clinically localized PC.