UROKINASE (UPA) AND PAI-1 PREDICT SURVIVAL IN ADVANCED OVARIAN-CANCERPATIENTS (FIGO-III) AFTER RADICAL SURGERY AND PLATINUM-BASED CHEMOTHERAPY

Fifty-one patients with advanced ovarian cancer FIGO III were studied to determine new tumor biology-oriented prognostic factors. The tumor- associated protease urokinase-type plasminogen activator (uPA) and its inhibitor PAI-1 were detected in malignant ovarian cancer tissue extr acts. The concentration of both factors was significantly higher in ma lignant tissue compared with benign ovarian tissue specimens (P < 0.01 ). According to a cutoff value for uPA and PAI-1, patients could be su bdivided into risk groups: patients with low uPA and PAI-1 (uPA < 0.9 ng/mg protein and PAI-1 < 13.5 ng/mg protein) had a statistically sign ificant better prognosis than patients with high uPA and/or high PAI-1 (P = 0.01). Especially in patients without residual tumor, uPA and PA I-1 were strong prognostic parameters (P = 0.03). In multivariate anal ysis the residual tumor was the most powerful prognostic indicator (P = 0.013) closely followed by uPA and PAI-I (P = 0.047). Moreover, ther e is a strong correlation between uPA levels and lymph node involvemen t (P = 0.004) and a trend to higher uPA-levels in poorly differentiate d (G3 + G4) cancers (P = 0.059) and in tumors with increased ascites p roduction (P = 0.09). A trend to higher PAI-1 levels was also noted in the above-mentioned tumor situations. The differences, however, were of no statistical significance. From these data it can be concluded th at the pattern of tumor spread (mainly intraabdominally versus additio nal extensive lymph node involvement) and tumor biological appearance (ascites production, differentiation) are reflected by the expression of the tumor-associated proteolytic factors uPA and PAI-1. Adjuvant th erapy might be adjusted to uPA and PAI-1 not only in advanced ovarian cancer but also in carcinoma of low malignant potential or early-stage ovarian carcinoma. (C) 1994 Academic Press, Inc.