Decreased stromal expression and increased epithelial expression of WFDC1/ps20 in prostate cancer is associated with reduced recurrence-free survival

Prostate. 2004 Oct 1;61(2):182-91. doi: 10.1002/pros.20085.

Abstract

Background: WAP-type four disulfide core (WFDC1)/ps20 is a member of the whey acidic protein family, which includes several serine protease inhibitors. Expression of WFDC1/ps20 was previously demonstrated in the normal human prostate stromal compartment. To further current understanding of the role of WFDC1/ps20 in prostate cancer, altered expression of WFDC1/ps20 protein in prostate cancer was evaluated.

Methods: Immunohistochemical staining for WFDC1/ps20 was performed using tissue microarrays. Quantitation was based on the percentage of positive-staining stromal or epithelial cells and staining intensity. Resulting data was analyzed relative to the recurrence-free survival data and additional information for this patient set.

Results: Decreased stromal expression of WFDC1/ps20 predicted shorter recurrence-free survival time by univariate analysis. Decreased stromal WFDC1/ps20 expression correlated with higher radical prostatectomy Gleason scores, positive surgical margins, extracapsular extension, higher clinical stage, and higher preoperative prostate specific antigen levels. Increased epithelial expression of WFDC1/ps20 also predicted shorter recurrence-free survival times by univariate analysis. Increased epithelial expression of WFDC1/ps20 correlated with higher biopsy and radical prostatectomy Gleason scores, and higher clinical stage.

Conclusions: Decreased stromal WFDC1/ps20 expression reflects the evolution of a prostate cancer reactive stroma, while increased epithelial WFDC1/ps20 expression may indicate progression to a more aggressive epithelial phenotype and may indicate an epithelial mesenchymal transition (EMT) process. Further evaluation of WFDC1/ps20 biologic functions will aid in the understanding of this interesting expression profile.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Disease-Free Survival
  • Epithelium / metabolism
  • Humans
  • Male
  • Neoplasm Recurrence, Local*
  • Predictive Value of Tests
  • Prostate / metabolism*
  • Prostatic Neoplasms / metabolism*
  • Protein Biosynthesis*
  • Proteins*
  • Survival Analysis

Substances

  • Proteins
  • WFDC1 protein, human