p53, p21, pRB, and p16 expression predict clinical outcome in cystectomy with bladder cancer. Academic Article uri icon

Overview

abstract

  • PURPOSE: To determine whether p53, p21, pRB, and/or p16 expression is associated with bladder cancer stage, progression, and prognosis. PATIENTS AND METHODS: Immunohistochemical staining for p53, p21, pRB, and p16 was carried out on serial sections from archival specimens of 80 patients who underwent bilateral pelvic lymphadenectomy and radical cystectomy for bladder cancer (median follow-up, 101 months). RESULTS: p53, p21, and pRB or p16 expression was altered in 45 (56%), 39 (49%), and 43 (54%) tumors, respectively. Sixty-six patients (83%) had at least one marker altered, and 21 patients (26%) had all three altered. Abnormal expressions of p53, p21, and pRB/p16 expression were associated with muscle-invasive disease (P=.007, P=.003, and P=.003, respectively). The alteration of each marker was independently associated with disease progression (P< or =.038) and disease-specific survival (P< or =.039). In multivariable models that included standard pathologic features and p53 with p21 or p53 with pRB/p16, only p53 and lymph node metastases were associated with bladder cancer progression (P< or =.026) and death (P< or =.028). In models that included p21 and pRB/p16, only p21 and lymph node metastases were associated with bladder cancer progression (P< or =.022) and death (P< or =.028). In a model that included the combined variables p53/p21 and pRB/p16, only p53/p21 and lymph node status were associated with bladder cancer progression (P< or =.047) and death (P< or =.036). The incremental number of altered markers was independently associated with an increased risk of bladder cancer progression (P=.005) and mortality (P=.007). CONCLUSION: Although altered expression of each of the four cell cycle regulators is associated with bladder cancer outcome in patients undergoing radical cystectomy, p53 is the strongest predictor, followed by p21, suggesting a more pivotal role of the p53/p21 pathway in bladder cancer progression.

publication date

  • February 23, 2004

Research

keywords

  • Biomarkers, Tumor
  • Carcinoma, Transitional Cell
  • Cyclin-Dependent Kinase Inhibitor p16
  • Cyclins
  • Cystectomy
  • Retinoblastoma Protein
  • Tumor Suppressor Protein p53
  • Urinary Bladder Neoplasms

Identity

Scopus Document Identifier

  • 1842457693

Digital Object Identifier (DOI)

  • 10.1200/JCO.2004.03.118

PubMed ID

  • 14981102

Additional Document Info

volume

  • 22

issue

  • 6