PLASMINOGEN-ACTIVATOR INHIBITOR-1 IS AN INDEPENDENT POOR PROGNOSTIC FACTOR FOR SURVIVAL IN ADVANCED-STAGE EPITHELIAL OVARIAN-CANCER PATIENTS

High levels of plasminogen activator inhibitor-I (PAI-I) in tissue ext racts have been associated with poor prognosis in many epithelial canc ers, Ovarian cancers contain a higher concentration of PAI-I than beni gn ovarian tumors or normal ovaries. Reports, however, on the prognost ic value of PAI-I content in ovarian cancers have been conflicting. We used immunohistochemistry to study the primary and metastatic tissues from 131 epithelial ovarian cancer cases, This group has been previou sly characterized for the expression of urokinase (uPA), uPA receptor, PAI-2 and macrophage colony-stimulating factor (CSF-I). The intensity and extent of staining for PAI-I in the tumor epithelium was scored. Kaplan-Meier curves of survival were compared using the log-rank test. The Cox regression model was utilized for multivariate analysis, Appr oximately 50% of the primary tumors and metastases expressed PAI-I, Am ong invasive stages III and IV patients, those whose primary tumors ex pressed PAI-I had a shorter overall survival, The combination of stron g expression of PAI-I and expression of uPA was a highly significant f actor for short disease free and overall survival. Similar results wer e seen with the combination of high PAI-I and low PAI-2 expression, St rong PAI-I expression was significantly associated with expression of uPA receptor or CSF-I in the tumor epithelium, but not with standard c linical parameters, and was an independent prognostic factor for poor survival on multivariate analysis, Our results show that PAI-I express ion in the primary tumor epithelium is an independent poor prognostic factor for survival, underscoring the tumor protective role of PAI-I i n ovarian cancer biology. Int. J. Cancer (Pred. Oncol.) 79:449-454, 19 98. (C) 1998 Wiley-Liss, Inc.