High Level PSMA Expression Is Associated With Early PSA Recurrence in Surgically Treated Prostate Cancer

BACKGROUND. Prostate specific membrane antigen (PSMA) is a suggested target for antibody-based therapy of prostate cancer potentially involved in the regulation of cell migration. This study was undertaken, to gain more insight on the role of PSMA in early prostate cancer and its distribution in various normal tissues. METHODS. A total of 1,700 different prostate cancers treated by radical prostatectomy and 612 samples from 76 different normal tissue types were successfully analyzed by immunohistochemistry (IHC) in a tissue microarray (TMA) format. PSMA immunostaining in cancers was also compared with clinical follow-up, preexisting HER2 expression and Ki67 labeling index data. RESULTS. PSMA staining was only found in prostate epithelium and expression was higher in cancer cells than in benign tissue. PSMA staining was found in 94.1% of cancers and was significantly associated with tumor stage, high Gleason grade, preoperative PSA, and HER2 expression (P<0.0001 each). Tumors with strong PSMA expression had a higher risk of biochemical recurrence than cancers with only weak PSMA staining intensity (P=0.0483). There was no significant association between PSMA expression and Ki67 labeling index (P=0.442). CONCLUSIONS. Based on the high frequency of PSMA overexpression in all stages and grades of prostate cancer and the high prevalence of PSMA overexpression, it can be speculated that increased PSMA expression may be related with prostate cancer development rather than progression. The known function of PSMA activating cell migration would be in line with the suggested role in cancer progression and the missing association between PSMA overexpression and tumor cell proliferation. Prostate 71: 281-288, 2011. (C) 2010 Wiley-Liss, Inc.