p53 accumulation associated with bcl-2, the proliferation marker MIB-1 and survival in patients with prostate cancer subjected to watchful waiting

J Urol. 2000 Sep;164(3 Pt 1):716-21. doi: 10.1097/00005392-200009010-00023.

Abstract

Purpose: We describe the association of p53 nuclear protein accumulation with bcl-2 expression, tumor cell proliferation and clinical outcome in a prostate cancer population undergoing watchful waiting.

Materials and methods: Immunohistochemical staining for p53 was semiquantitatively scored in archival formalin fixed, paraffin embedded tumor tissue obtained at diagnosis in 221 patients with prostate cancer. At a median of 15 years followup was nearly complete. Eventually 57% of the patients died of prostate cancer.

Results: p53 Immunohistochemical staining was heterogeneous but in all cases at least clusters of tumor cells had nuclear staining for p53. The percent of p53 immunoreactive tumor cells was scored as 0 to 4+ in p53 positive hot spots. p53 immunoreactivity correlated with clinical stage and histopathological grade (p = 0.003 and 0.009, respectively). When dichotomized into low (0% to 50%) and high (51% to 100%) immunoreactivity groups of 40 and 181 patients, respectively, p53 accumulation was significantly associated with disease specific survival in the study population overall (p <0. 0001) and in the 125 with clinically localized disease (p = 0.0002). p53 Immunoreactivity was significantly (p <0.001) associated with the proliferation marker MIB-1 (median value 10.3, range 0 to 46.1) but insignificantly (p = 0.8) correlated with bcl-2 expression (52% positive). However, patients with combined favorable MIB-1 and bcl-2 status were stratified into significant (p = 0.02) prognostic groups by p53 immunohistochemical status. Multivariate analysis revealed that p53 immunoreactivity was a significant prognostic factor in patients with clinically localized prostate cancer (p <0.0001).

Conclusions: p53 Nuclear protein accumulation detected by immunohistochemical study was an independent adverse prognostic factor in patients with prostate cancer undergoing watchful waiting.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antigens, Nuclear
  • Biomarkers, Tumor / analysis*
  • Cause of Death
  • Cell Division
  • DNA-Binding Proteins / analysis*
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry
  • Ki-67 Antigen
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Staging
  • Nuclear Proteins / analysis*
  • Prognosis
  • Proportional Hazards Models
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / pathology
  • Proto-Oncogene Proteins c-bcl-2 / analysis*
  • Survival Rate
  • Treatment Outcome
  • Tumor Suppressor Protein p53 / analysis*

Substances

  • Antigens, Nuclear
  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • Ki-67 Antigen
  • Nuclear Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Tumor Suppressor Protein p53