Urokinase (uPA) and PAI-1 Predict Survival in Advanced Ovarian Cancer Patients (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 extracts. The concentration of both factors was significantly higher in malignant tissue compared with benign ovarian tissue specimens (P < 0.01). According to a cutoff value for uPA and PAI-1, patients could be subdivided 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 significant better prognosis than patients with high uPA and/or high PAI-1 (P = 0.01). Especially in patients without residual tumor, uPA and PAI-1 were strong prognostic parameters (P = 0.03). In multivariate analysis the residual tumor was the most powerful prognostic indicator (P = 0.013) closely followed by uPA and PAI-1 (P = 0.047). Moreover, there is a strong correlation between uPA levels and lymph node involvement (P = 0.004) and a trend to higher uPA-levels in poorly differentiated (G3 + G4) cancers (P = 0.059) and in tumors with increased ascites production (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 that the pattern of tumor spread (mainly intraabdominally versus additional 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 therapy 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.