Evaluation of urokinase plasminogen activator and its receptor in different grades of human prostate cancer

Increased expression of urokinase plasminogen activator (uPA) and its receptor (uPAR) has been reported in various malignancies including prostate cancer (CaP). However, their expression in the different grades of CaP remains poorly understood. Here, we use tissue microarrays to examine the expression of uPA and uPAR in different grades of human CaP and to establish the potential of these tumor-associated antigens as candidates for targeted therapy. One hundred twenty paraffin-embedded specimens were selected from patients who underwent radical retropubic prostatectomy or transurethral resection of the prostate for primary untreated CaP and 10 matched lymph node metastases. Monoclonal antibodies #394 and #3936 were used on tissue microarrays with standard immunohistochemistry to examine uPA and uPAR expression, respectively. Overexpression of uPA and uPAR was detected in 53% and 64% of primary CaP tissues, respectively, and in more than 90% of lymph node metastases, but not in normal prostates or benign tissues. Of the uPA and uPAR positive tumors, 76% and 68% were Gleason score 7 or higher, respectively, and most of these tumors also showed stromal staining. The overexpression of uPA and uPAR was highly related to tumor differentiation in patients with CaP. Both uPA and uPAR proteins are candidate therapeutic targets for cancer therapy to control micrometastases and hormone refractory disease in CaP.