Elevated Levels of Apoptosis Regulator Proteins P53 and BCL-2 are Independent Prognostic Biomarkers in Surgically Treated Clinically Localized Prostate Cancer

Abstract

The tumor suppressor gene (TSG) p53 and the proto-oncogene bcl-2 have been shown to be involved in the regulation of cell growth and apoptosis and have been implicated in hormone refractory prostate cancer (PC) and poor prognosis. The goal of this study was to determine the clinical utility of the presence of p53 and bcl-2 immunohistochemical (IHC) protein in the primary tumor as predictors of disease progression following radical prostatectomy (RP). The expression of p53 and bcl-2 was evaluated in archival paraffin-embedded RP specimens from 175 patients followed from 1 to 9 years (mean = 4.6 years) and correlated with stage, grade, race and serologic (PSA) recurrence following surgery. Overexpression of bcl-2 was noted in 47 of 175 (26.9 percent) patients; these patients had a significantly higher 5-year failure rate than those who did not overexpress bcl-2 (67.0 percent versus 30.7 percent). Expression of p53 was noted in 114 of 175 (65.1 percent) patients with a 5-year failure rate of 51.1 percent compared with a 5-year failure rate of only 22 percent in p53 negative patients. When expression rates for p53 and bcl-2 were combined, the 5-year failure rate was 75.3 percent. Conversely, when both p53 and bcl-2 IHC staining were negative, the 5-year failure rate was 20.4 percent. Univariate Kaplan-Meier analysis showed a statistically significant difference between p53 and bcl-2 positive and negative patients (p less than 0.001). Multivariate Cox Regression Analysis with backward elimination controlling for age, race, stage and grade showed both p53 (p = .0185) and bcl-2 (p = .044) to be independent predictors of disease-free survival. p53 and bcl-2 appear to be important biomarkers that predict recurrence in clinically localized PC after RP.