Prognostic significance of urokinase (uPA) and its inhibitor PAI-1 for survival in advanced ovarian carcinoma stage FIGO IIIc

Strong evidence has accumulated on the prognostic value of tumour-associated proteolytic factors in patients afflicted with solid malignant tumours, including advanced ovarian cancer. We evaluated the prognostic impact of the protease urokinase plasminogen activator (uPA) and its inhibitor PAI-I on overall survival in patients with advanced ovarian cancer stage FIGO IIIc in order to select patients at risk, uPA and PAI-I antigen were determined by ELISA in primary tumour tissue extracts of 86 ovarian cancer patients FIGO stage IIIc enrolled in a prospective study. Univariate and multivariate analyses were performed using the Cox proportional hazard model. The time-varying coefficient model of Gray was used to assess the time-dependent strength of prognostic factors tumour mass, uPA and PAI-I on overall survival. In all patients, uPA and PAI-I (optimized cut-offs of 2.0 and 27.5 ng mg(-1) protein respectively), in addition to the traditional prognostic parameters of residual tumour mass, nodal status, grading and ascites volume, were of prognostic significance in univariate analysis for overall survival. Even in patients with residual tumour mass (n = 43), the statistically independent prognostic impact of PAI-1 persisted, allowing further discrimination between low- and high-risk patients. In multivariate analysis, residual tumour mass (P < 0.001, relative risk (RR) 4.5), PAI-1 (P < 0.001; RR 3.1) and nodal status (P = 0.022, RR 2.6) turned out to be strong, statistically independent prognostic parameters. Evaluation of the time-dependent prognostic impact of residual tumour mass and PAI-I on overall survival (n = 86, 50 months) revealed that the prognostic power of these factors increased with time. In patients with advanced ovarian cancer, both residual tumour mass and PAI-I are statistically independent strong prognostic factors. Even within patient subgroups with or without residual tumour mass, PAI-1 allowed selection of patients at risk who might benefit from individualized therapy protocols.