Overexpression of the Plasminogen Activator Inhibitor Type-1 in Epithelial Ovarian Cancer

Abstract

Background: The plasminogen activator-plasmin cascade plays a central role in the progression of solid tumors. The type-1 plasminogen activator inhibitor (PAI-1) is the major physiological regulator of plasminogen activation. PAI-1 is suggested to play a crucial role in tumor cell invasion and metastasis of various solid tumors. The aim of this study was to analyze the clinical and prognostic roles of PAI-1 in epithelial ovarian cancer (OC). Materials and Methods: Expression analysis was conducted by immunohistochemistry and ELISA. Tissue sections of paraffin-embedded tumor specimens and fresh-frozen tumor samples from patients with benign and malignant ovarian tumors (OT), who had undergone surgical intervention in the Department of Gynaecology and Obstetrics, Charité, Germany, from 02/01 to 06/02, were used. Correlation analysis with conventional clinical factors, univariate and multivariate analyses were performed using SPSS (SPSS Inc., V.11.0). Results: Sixty-five patients (31 primary OC, 20 recurrent OC, 4 low-malignant potential OT, 6 benign OT, 4 normal ovary) were allocated to this trial. The median age was 57 years (range, 34-86) and the median follow-up was 20 months (range, 0-64). The distributions of (FIGO) tumor stage of all primary OC were: I=16.1%, II=3.2%, III=45.2% and IV=35.5%. PAI-1 was significantly overexpressed in the tumor epithelium of OC in comparison to the ovarian epithelium of benign OT and normal ovary (p<0.001). The median PAI-1 level was 1.92-fold higher in malignant OT than in benign OT. Statistical analyses showed no significant correlation between the expression of PAI-1 and clinical parameters. The expression of PAI-1 and the PAI-1 level, according to 3 different cut-off values, showed no prognostic impact in univariate analysis. In multivariate analysis, only tumor stage (FIGO) (p=0.003) and residual tumor (p=0.009) remained independent prognostic factors for post-operative survival. Conclusion: PAI-1 is significantly overexpressed in OC.