Prognostic value of PTEN loss in men with conservatively managed localised prostate cancer

Br J Cancer. 2013 Jun 25;108(12):2582-9. doi: 10.1038/bjc.2013.248. Epub 2013 May 21.

Abstract

Background: The natural history of prostate cancer is highly variable and difficult to predict. We report on the prognostic value of phosphatase and tensin homologue (PTEN) loss in a cohort of 675 men with conservatively managed prostate cancer diagnosed by transurethral resection of the prostate.

Methods: The PTEN status was assayed by immunohistochemistry (PTEN IHC) and fluorescent in situ hybridisation (PTEN FISH). The primary end point was death from prostate cancer.

Results: The PTEN IHC loss was observed in 18% cases. This was significantly associated with prostate cancer death in univariate analysis (hazard ratio (HR)=3.51; 95% CI 2.60-4.73; P=3.1 × 10(-14)). It was highly predictive of prostate cancer death in the 50% of patients with a low risk score based on Gleason score, PSA, Ki-67 and extent of disease (HR=7.4; 95% CI 2.2-24.6; P=0.012) ), but had no prognostic value in the higher risk patients. The PTEN FISH loss was only weakly associated with PTEN IHC loss (κ=0.5). Both PTEN FISH loss and amplification were univariately predictive of death from prostate cancer, but this was not maintained in the multivariate analyses.

Conclusion: In low-risk patients, PTEN IHC loss adds prognostic value to Gleason score, PSA, Ki-67 and extent of disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / diagnosis*
  • Adenocarcinoma / genetics
  • Adenocarcinoma / mortality
  • Adenocarcinoma / surgery
  • Adult
  • Aged
  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / metabolism
  • Gene Expression Regulation, Neoplastic
  • Gene Silencing / physiology
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Ki-67 Antigen / metabolism
  • Male
  • Middle Aged
  • Neoplasm Grading
  • PTEN Phosphohydrolase / genetics*
  • PTEN Phosphohydrolase / metabolism
  • Predictive Value of Tests
  • Prognosis
  • Prostate-Specific Antigen / metabolism
  • Prostatic Neoplasms / diagnosis*
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / mortality
  • Prostatic Neoplasms / surgery
  • Transurethral Resection of Prostate

Substances

  • Biomarkers, Tumor
  • Ki-67 Antigen
  • PTEN Phosphohydrolase
  • PTEN protein, human
  • Prostate-Specific Antigen