p53 and p21 Expression levels predict organ preservation and survival in invasive bladder carcinoma treated with a combined-modality approach

Cancer. 2004 May 1;100(9):1859-67. doi: 10.1002/cncr.20200.


Background: The purpose of the current study was to evaluate the expression levels of p53, p21 and pRB as predictors of for long-term organ preservation and survival in patients with bladder carcinoma who were treated with bladder-sparing intent using a combined-modality approach.

Methods: Tumor samples from 82 consecutive patients with localized invasive bladder carcinoma treated on 3 different bladder-sparing studies were examined for p53, p21, and pRB expression by immunohistochemical methods. Treatment consisted of transurethral resection, platinum-based neoadjuvant chemotherapy, and, according to response, either radiotherapy or radical cystectomy. The median follow-up duration was 55 months.

Results: Positive immunoreactivity for p53, p21, and pRB was observed in 47%, 52%, and 67% of patients, respectively. Positive p53 immunoreactivity and positive p21 immunoreactivity were independent predictors of decreased survival with bladder preservation (P = 0.02 and P = 0.02, respectively) and disease-free survival (DFS; P = 0.005 and P = 0.009, respectively) in a multivariate analysis adjusting for clinical stage, ureteral obstruction, and age. Regarding overall survival (OS), p53 overexpression was associated with poor outcome (P = 0.03), whereas the association of poor outcome with p21 expression did not reach statistical significance (P = 0.07). No association between pRB immunoreactivity and outcome was found. When the combined expression of p53 and p21 was assessed, the positive expression of both markers was a strong and unfavorable prognostic factor for survival with bladder preservation (P = 0.006), DFS (P = 0.003), and OS (P = 0.02).

Conclusions: Expression levels of p53 and p21, especially when simultaneously assessed, exhibit independent predictive value for long-term bladder preservation and survival in patients with bladder carcinoma treated with combined-modality therapy. These determinations could be useful in the selection of candidates for bladder-preserving treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / analysis*
  • Biopsy, Needle
  • Carcinoma, Transitional Cell / genetics*
  • Carcinoma, Transitional Cell / mortality*
  • Carcinoma, Transitional Cell / therapy
  • Chemotherapy, Adjuvant
  • Combined Modality Therapy
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Invasiveness / pathology*
  • Neoplasm Staging
  • Predictive Value of Tests
  • Probability
  • Prognosis
  • Proportional Hazards Models
  • Radiotherapy, Adjuvant
  • Retrospective Studies
  • Risk Assessment
  • Survival Analysis
  • Transurethral Resection of Prostate / methods
  • Treatment Outcome
  • Tumor Suppressor Protein p53 / genetics*
  • Urinary Bladder Neoplasms / genetics*
  • Urinary Bladder Neoplasms / mortality*
  • Urinary Bladder Neoplasms / therapy


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