Expression and prognostic significance of urokinase and plasminogen activator inhibitor type-1 in endometrial hyperplasia and cancer

Proteolytic enzymes, like urokinase (uPA) and plasminogen activator inhibit or type-1 (PAI-1), are involved in remodelling tissues during invasion and metastasis of tumor cells. The purpose of the study is to evaluate the expr ession and the prognostic significance of these enzymes in endometrial hype rplasia and cancer. We used immunohistochemical staining to localize uPA an d PAI-1 antigens and evaluate their expression, and the enzyme-linked immun osorbent assay (ELISA) to measure their levels during the progression of en dometrial carcinoma. The results show that the levels of uPA and PAI-1 detection are systematica lly weak in simplex hyperplasia and are moderate in complex hyperplasia. in the endometrial carcinoma a very strong reaction was observed in the most aggressive variant of epithelial tumors. A positive signal for uPA was foun d only in the cytoplasm of normal and hyperplastic cells while, in tumors, uPA was present also in the cellular areas surrounding the neoplastic gland s and at the apex of the malignant cells. The PAI-1 immunoreactivity was we ak to moderate in 95.4 % of carcinomas, with a diffuse signal mostly distri buted in the cytoplasm of neoplastic cells and tumor stroma. UPA antigen co ncentrations were significantly higher in endometrial carcinoma than in end ometrial hyperplasia (p <0.05) and in normal endometrium (p <0.001). PAI-1 antigen concentrations in carcinoma samples were significantly higher than in normal endometrium (p=0.002), but the difference was nor statistically s ignificant with respect to that in endometrial hyperplasia. We did not find any correlation between uPA and PAI-1 concentrations and the standard prog nostic parameters for evaluating endometrial carcinoma. In conclusion, this study demonstrates that in hyperplastic endometria and in endometrial carc inoma there is a progressive increase in expression of uPA and PAI-1 than i n normal endometrial tissue. In carcinoma tissues, the high expression of u PA is unregulated in the surrounding stroma tissue, particularly in the mos t aggressive histopathologic variants. UPA and PAI-1 may be factors associa ted with invasive behavior in endometrial carcinoma independent of other cl inicopathological parameters.