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

Abstract

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. 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. 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. 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.