Relationship of p21(WAF-1) protein expression with prognosis in advanced prostate cancer treated by androgen ablation

OBJECTIVES. The objectives of our study were (1) to characterize the expres sion of p21 and p53 proteins in advanced stage prostate cancer, (2) to dete rmine the relationship between p53 and p21 protein expressions, and (3) to relate p53 and p21 expression to clinical outcome after androgen ablation. METHODS. Seventy-five patients with advanced prostate cancer (clinical stag e C: 11, stage D1: 8, stage D2: 56), who all underwent androgen ablation, h ad tissue specimens obtained prior to hormonal therapy and studied immunohi stochemicaly for p53 (Mab D07) and p21 (Mab EA10) expression. Clinical outc ome was analyzed using the Kaplan-Meier method and log-rank tests. Cox prop ortional hazard model was used to determine the independence of multiple va riables. RESULTS. About 33.3% of cases expressed p53 and 33.3% expressed p21 positiv e immunoreactivity. No statistically significant correlation between p21 an d p53 expression either in the entire study group (N = 75) or in stage D2 c ases (N = 56) was observed (P = 0.38 and P = 0.68, respectively). Disease-s pecific survival was significantly related to p21 expression (P = 0.0006 fo r 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 a nd the number of bone lesions were independently associated with shorter su rvival (multivariate P = 0.001, P = 0.005, respectively). CONCLUSIONS. The data suggests that p21 expression is a strong and independ ent poor prognostic factor in patients with advanced stage prostate cancer treated by androgen ablation. (C) 2001 Wiley-Liss, Inc.