Plasminogen activator inhibitor type 2: potential prognostic factor for endometrial carcinomas

The clinical determination of proteases which are involved in carcinogenesis, invasion and metastasis may contribute to the detection of the early stage of disease, and to the prognostic assessment of patients with the cancer. The aim of the present study was to determine the level of urokinase plasminogen activator (uPA), plasminogen activator inhibitor type 1 (PAI-1) and plasminogen activator inhibitor type 2 (PAI-2) in normal and malignant tissues of corpus uteri and to evaluate the possible correlation with clinical and histopathological prognostic factors. UPA, PA-I and PAI-2 were determined by the ELISA assay in tissue cytosol of matched pair samples from 27 patients with endometrial carcinoma. Results show that significantly higher levels of these proteins were found in malignant than in normal tissue samples (uPA: 1.266 versus 0.633 ng/mg protein, PAI-1:4.468 versus 1.958 ng/mg protein, and PAI-2:3.428 versus 0.483 ng/ml protein). The levels of uPA and PAI-1 did not correlate with clinical staging or pathohistological grading. However, in tumor tissues with clinical stages II and III, myometrial invasion > 50%, and lymphovascular invasion, increased levels of PAI-2 were determined. Our results indicate that components of the plasminogen activation cascade are up-regulated in endometrial cancer and suggest the role of PAI-2 in determining invasive potential of endometrial carcinomas.