EXPRESSION OF PLASMINOGEN-ACTIVATOR INHIBITOR-2 IN EPITHELIAL OVARIAN-CANCER - A FAVORABLE PROGNOSTIC FACTOR-RELATED TO THE ACTIONS OF CSF-1

In ovarian cancer cells, the macrophage colony-stimulating factor-I (C SF-I) induces the release of plasminogen activator inhibitor-2 (PAI-2) , and high levels of PAI-2 as well as of CSF-I in ovarian cancer ascit es are independently correlated with poor outcome. We now study the ef fect of CSF-I on PAI-2 expression in vitro and the significance of cel lular PAI-2 expression in vivo, Immunohistochemical detection of PAI-2 was studied in primary and metastatic tissues from 130 epithelial ova rian cancer cases, Kaplan-Meier curves of survival were compared with the results of log-rank test. The Cox regression model was used for mu ltivariate analysis, The effect of CSF-I on PAI-2 expression in ovaria n cancer cells was also examined in vitro, Fifty-eight percent of the primary tumors and 68% of the metastases expressed PAI-2. PAI-2 expres sion in the metastases of invasive stages III and IV cases was strongl y predictive of a prolonged disease-free and overall survival, This fi nding was associated with low residual disease and was also an indepen dent factor for disease-free survival, In vitro, CSF-I treatment of ov arian cancer cells resulted in a decrease in cellular staining for PAI -2 while increasing the release of PAI-2 into the conditioned medium, In vivo, we also found an inverse correlation between expression of CS F-I and that of PAI-2 in the primary tumors, We thus describe the favo rable independent prognosis of cellular PAI-2 expression in the metast ases of ovarian cancer, Moreover, an inverse correlation was observed between CSF-I and PAI-2 expression in vivo. This lends support for a p rimary role of cell-surface (vs. secreted)-mediated events of plasmino gen activation in the development of invasive, poor prognostic phenoty pes. (C) 1997 Wiley-Liss, Inc.