Role of urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor type 1 (PAI-1) for prognosis in endometrial cancer

Abstract Background. Urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor type 1 (PAI-1) contribute to the invasiveness of many carcinomas. Here, we studied a possible association between cytosolic uPA and PA-1 concentrations in tumor tissue with prognosis in patients with endometrial cancer. Methods. Cytosolic concentrations of uPA and PAI-1 were determined in 69 primary endothelial adenocarcinomas using an enzyme-linked immunoassay (ELISA). A possible influence of uPA and PAI-1 was studied by multivariate Cox regression adjusting for the established clinical prognostic factors FIGO-stage, grading, depth of invasion, diabetes mellitus and age. Results. Both uPA ( p = 0.011) and PAI-1 ( p = 0.003) were associated with relapse free time using the multivariate proportional hazards model. Association with overall survival was less pronounced with p = 0.021 for uPA and p = 0.358 for PAI-1. Concentrations of PAI-1 increased with FIGO stage ( p = 0.003) and with histological grading ( p = 0.005). Both uPA and PAI-1 concentrations were negatively correlated with estrogen and progesterone receptor levels. Conclusion. The combination of high cytosolic concentrations of uPA (N 5 ng/mg total protein) and high PAI-1 (N 20 ng/mg total protein) may reveal a group of patients with increased risk of progression