Expression of p53, p21 and cyclin D1 in penile cancer: p53 predicts poor prognosis

J Clin Pathol. 2012 Mar;65(3):232-6. doi: 10.1136/jclinpath-2011-200429. Epub 2011 Dec 1.

Abstract

Aims: To evaluate the role of p53, p21 and cyclin D1 expression in patients with penile cancer (PC).

Methods: Paraffin-embedded tissues from PC specimens from six pathology departments were subjected to a central histopathological review performed by one pathologist. The tissue microarray technique was used for immunostaining which was evaluated by two independent pathologists and correlated with cancer-specific survival (CSS). κ-statistics were used to assess interobserver variability. Uni- and multivariable Cox proportional hazards analysis was applied to assess the independent effects of several prognostic factors on CSS over a median of 32 months (IQR 6-66 months).

Results: Specimens and clinical data from 110 men treated surgically for primary PC were collected. p53 staining was positive in 30 and negative in 62 specimens. κ-statistics showed substantial interobserver reproducibility of p53 staining evaluation (κ=0.73; p<0.001). The 5-year CSS rate for the entire study cohort was 74%. Five-year CSS was 84% in p53-negative and 51% in p53-positive PC patients (p=0.003). Multivariable analysis showed p53 (HR=3.20; p=0.041) and pT-stage (HR=4.29; p<0.001) as independent significant prognostic factors for CSS. Cyclin D1 and p21 expression were not correlated with survival. However, incorporating p21 into a multivariable Cox model did contribute to improved model quality for predicting CSS.

Conclusions: In patients with PC, the expression of p53 in the primary tumour specimen can be reproducibly assessed and is negatively associated with cancer specific survival.

Publication types

  • Multicenter Study

MeSH terms

  • Biomarkers, Tumor / analysis*
  • Chi-Square Distribution
  • Cyclin D1 / analysis*
  • Cyclin-Dependent Kinase Inhibitor p21 / analysis*
  • Disease-Free Survival
  • Germany
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Male
  • Multivariate Analysis
  • Paraffin Embedding
  • Penile Neoplasms / chemistry*
  • Penile Neoplasms / mortality
  • Penile Neoplasms / pathology
  • Penile Neoplasms / surgery
  • Predictive Value of Tests
  • Prognosis
  • Proportional Hazards Models
  • Reproducibility of Results
  • Retrospective Studies
  • Risk Assessment
  • Risk Factors
  • Survival Rate
  • Time Factors
  • Tissue Array Analysis
  • Treatment Outcome
  • Tumor Suppressor Protein p53 / analysis*

Substances

  • Biomarkers, Tumor
  • CCND1 protein, human
  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Cyclin D1