Elevation of urokinase-type plasminogen activator and its receptor densities as new predictors of disease progression and prognosis in men with prostate cancer.

Abstract

We examined whether two newly defined parameters, the density of urokinase-type plasminogen activator (uPAD) and the density of its receptor (uPARD), which were determined by dividing the serum levels of uPA and uPAR by the prostate volume, respectively, could be used as predictors of the progression and prognosis of prostate cancer (PC). Serum levels of uPA and uPAR in 40 healthy controls, 70 patients with benign prostatic hypertrophy (BPH) and 80 patients with PC were measured by a sandwich enzyme immunoassay, and prostate volume was measured by ultrasonography. The mean levels of uPAD and uPARD in patients with PC were significantly higher than those in healthy controls and patients with BPH. Furthermore, the uPAD and uPARD levels in PC patients with metastasis were significantly elevated compared with those in patients without metastasis. Among patients who underwent radical prostatectomy, the levels of uPAD and uPARD in patients with pathologically organ-confined disease were significantly lower than in those with advanced disease. The overall survival rate of PC cancer patients with elevated levels of either uPAD or uPARD, or of both, was significantly lower than that of patients with normal levels of uPAD and uPARD. In addition, Cox's multivariate analysis revealed that the elevation of uPAD or uPARD level, or of both, was strongly associated with overall survival in PC patients. These findings suggest that the elevation of uPAD or uPARD, or of both, could be used as new predictors of progression and prognosis in patients with PC.