Association of urokinase-type plasminogen activator and its inhibitor withdisease progression and prognosis in ovarian cancer

Purpose: Urokinase-type plasminogen activator (uPA) and its inhibitor, plas minogen activator inhibitor (PAI)-1, have been shown to be related to poor prognosis in a variety of malignant solid tumors. Studies on the prognostic relevance of uPA and PAI-1 in ovarian cancer, however, have been inconclus ive. The current study tests the hypothesis that elevated expression of uPA and PAI-1 is associated with prognosis and disease progression, Experimental Design: uPA and PAI-1 were prospectively measured by quantitat ive ELISA in tumor samples from 103 ovarian cancer patients (82 primary inv asive epithelial carcinomas, 9 low malignant potential tumors, and 12 recur rent ovarian carcinomas), Results: uPA but not PAI-1 levels were consistently associated with maligna nt progression, with levels increased from low malignant potential tumors t o primary tumors (uPA, P = 0.03; PAI-1, P = 0.019), from early to advanced disease stages (uPA, P = 0.014; PAI-I, P = 0.23), and from primary to intra -abdominal metastatic tumors (uPA, P = 0.001; PAI-1, P = 0.16). High uPA an d PAI-1 levels were associated with residual tumor volumes of >1 cm (P = 0. 001 and P = 0.016, respectively), Among invasive International Federation o f Gynecologists and Obstetrician stages I-IV tumors, elevated levels of uPA (>5.5 ng/mg) and PAI-I (> 18.8 ng/ml) were associated with a shortened pro gression-free survival (uPA, P = 0.003; PAI-1, P = 0.039) and overall survi val (uPA, P = 0.0002; PAI-1, P = 0.007). In multivariate analysis, uPA reta ined prognostic independence for progression-free survival (P = 0.037) and overall survival (P = 0.006). Conclusions: These data suggest that the uPA/PAI-1 axis may play an importa nt role in the intra-abdominal spread and reimplantation of ovarian cancer cells, The prognostic relevance of uPA and PAI-1 supports their possible ro le in the malignant progression of ovarian cancer.