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-1 (PAI-1) in tissue extracts have been associated with poor prognosis in many epithelial cancers. Ovarian cancers contain a higher concentration of PAI-1 than benign ovarian tumors or normal ovaries. Reports, however, on the prognostic value of PAI-1 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 previously characterized for the expression of urokinase (uPA), uPA receptor, PAI-2 and macrophage colony-stimulating factor (CSF-1). The intensity and extent of staining for PAI-1 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. Approximately 50% of the primary tumors and metastases expressed PAI-1. Among invasive stages III and IV patients, those whose primary tumors expressed PAI-1 had a shorter overall survival. The combination of strong expression of PAI-1 and expression of uPA was a highly significant factor for short disease-free and overall survival. Similar results were seen with the combination of high PAI-1 and low PAI-2 expression. Strong PAI-1 expression was significantly associated with expression of uPA receptor or CSF-I in the tumor epithelium, but not with standard clinical parameters, and was an independent prognostic factor for poor survival on multivariate analysis. Our results show that PAI-1 expression in the primary tumor epithelium is an independent poor prognostic factor for survival, underscoring the tumor protective role of PAI-1 in ovarian cancer biology.
Department of Obstetrics and Gynecology, Yale University School of Medicine, New Haven, CT 06520-8063, USA.
S K
SK
Chambers
C M
CM
Ivins
M L
ML
Carcangiu
D014408:Biomarkers, Tumor / Q000032:analysis*; D004848:Epithelium / Q000737:chemistry; D005260:Female; D006801:Humans; D016173:Macrophage Colony-Stimulating Factor / Q000032:analysis; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000737:chemistry* / Q000401:mortality* / Q000473:pathology; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis*; D017396:Plasminogen Activator Inhibitor 2 / Q000032:analysis; D011379:Prognosis; D011956:Receptors, Cell Surface / Q000032:analysis; D055293:Receptors, Urokinase Plasminogen Activator; D015996:Survival Rate; D014568:Urokinase-Type Plasminogen Activator / Q000032:analysis
D014408:Biomarkers, Tumor; C524898:PLAUR protein, human; D017395:Plasminogen Activator Inhibitor 1; D017396:Plasminogen Activator Inhibitor 2; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D016173:Macrophage Colony-Stimulating Factor; D014568:Urokinase-Type Plasminogen Activator