Decreased stromal expression and increased epithelial expression of WFDC1/ps20 in prostate cancer is associated with reduced recurrence-free survival.
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.
McAlhany
Stephanie J
SJ
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, USA.
Ayala
Gustavo E
GE
Frolov
Anna
A
Ressler
Steven J
SJ
Wheeler
Thomas M
TM
Watson
J E Vivienne
JE
Collins
Colin
C
Rowley
David R
DR
D018572:Disease-Free Survival; D004848:Epithelium / Q000378:metabolism; D006801:Humans; D008297:Male; D009364:Neoplasm Recurrence, Local; D011237:Predictive Value of Tests; D011467:Prostate / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000378:metabolism*; D014176:Protein Biosynthesis; D011506:Proteins; D016019:Survival Analysis
D011506:Proteins; C484310:WFDC1 protein, human