Combined p21WAF1/CIP1 and p53 overexpression predict improved survival in muscle-invasive bladder cancer treated by radical radiotherapy

Int J Radiat Oncol Biol Phys. 2001 Dec 1;51(5):1234-40. doi: 10.1016/s0360-3016(01)01801-6.

Abstract

Purpose: The prognostic value of p21 and p53 expression was evaluated for patients with muscle-invasive bladder cancer treated by radical radiotherapy.

Methods and materials: Sixty-eight paraffin-embedded sections from surgically resected tumors taken prior to irradiation were immunostained for p21 and p53.

Results: Nuclear staining for p21 and p53 was demonstrated in 32/68 (47%) and 46/68 (68%) tumors, respectively. There was no correlation between p21 and 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 p21-p53+ tumors (p = 0.0031), 29% for p21+p53- tumors (p = 0.0108); and 45% for p21-p53- tumors (p = 0.0375). The p21+p53+ group also demonstrated significantly improved survival when a combined analysis was performed of p21-p53+, 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 independent predictors of improved survival.

Conclusions: With muscle-invasive bladder tumors treated by radical radiotherapy, stratification for p21 and p53 identifies distinct prognostic groups, with p21+p53+ tumors being associated with the best survival and p21-p53+ the worst.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins / analysis*
  • Female
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Regression Analysis
  • Tumor Suppressor Protein p53 / analysis*
  • Urinary Bladder Neoplasms / chemistry
  • Urinary Bladder Neoplasms / mortality
  • Urinary Bladder Neoplasms / radiotherapy*

Substances

  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • Tumor Suppressor Protein p53