Relationship of p21(WAF-I) protein expression with prognosis in advanced prostate cancer treated by androgen ablation.

Abstract

The objectives of our study were (1) to characterize the expression of p21 and p53 proteins in advanced stage prostate cancer, (2) to determine the relationship between p53 and p21 protein expressions, and (3) to relate p53 and p21 expression to clinical outcome after androgen ablation. Seventy-five patients with advanced prostate cancer (clinical stage C: 11, stage D1: 8, stage D2: 56), who all underwent androgen ablation, had tissue specimens obtained prior to hormonal therapy and studied immunohistochemicaly for p53 (Mab D07) and p21 (Mab EA10) expression. Clinical outcome was analyzed using the Kaplan-Meier method and log-rank tests. Cox proportional hazard model was used to determine the independence of multiple variables. About 33.3% of cases expressed p53 and 33.3% expressed p21 positive immunoreactivity. No statistically significant correlation between p21 and p53 expression either in the entire study group (N = 75) or in stage D2 cases (N = 56) was observed (P = 0.38 and P = 0.68, respectively). Disease-specific survival was significantly related to p21 expression (P = 0.0006 for entire study group and P = 0.01 for D2 cases). There was no statistically significant differences in disease-specific survival between p53 positive or negative cases (P = 0.38 overall, P = 0.7 stage D2 only). p21 expression and the number of bone lesions were independently associated with shorter survival (multivariate P = 0.001, P = 0.005, respectively). The data suggests that p21 expression is a strong and independent poor prognostic factor in patients with advanced stage prostate cancer treated by androgen ablation.