Combined p21(WAF1/CIP1) and p53 overexpression predict improved survival in muscle-invasive bladder cancer treated by radical radiotherapy

Purpose: The prognostic value of p21 and p53 expression was evaluated for p atients with muscle-invasive bladder cancer treated by radical radiotherapy . Methods and Materials: Sixty-eight paraffin-embedded sections from surgical ly resected tumors taken prior to irradiation were immunostained for p21 an d p53. Results: Nuclear staining for p21 and p53 was demonstrated in 32/68 (47%) a nd 46/68 (68%) tumors, respectively. There was no correlation between p21 a nd p53 immunopositivity in this group (r = 0.067, p = 0.56). Patients were stratified into four distinct groups depending on staining for p21 and p53: p21+p53+, p21+p53-, p21-p53+, and p21-p53-. Patients with p21+p53+ tumors had the best prognosis with a 3-year survival of 82% compared to 12% for p2 1-p53+ tumors (p = 0.0031), 29% for p21+p53- tumors (p = 0.0108); and 45% f or p21-p53- tumors (p = 0.0375). The p21+p53+ group also demonstrated signi ficantly improved survival when a combined analysis was performed of p21-p5 3+, p21-p53-, and p21+p53- tumors (3-year survival = 30%, p = 0.0062). In a multivariate model, p21+p53+ tumors (p = 0.0108, relative risk [RR] = 5.18 ) and complete/partial response (p = 0.0019, RR = 3.76) were the only indep endent predictors of improved survival. Conclusions: With muscle-invasive bladder tumors treated by radical radioth erapy, stratification for p21 and p53 identifies distinct prognostic groups , with p21+p53+ tumors being associated with the best survival and p21-p53 the worst. (C) 2001 Elsevier Science Inc.