Clinical relevance of urokinase-type plasminogen activator, its receptor, and its inhibitor type 1 in endometrial cancer

Objective. Tumor invasion involves degradation of extracellular matrix. The urokinase plasminogen activation system participates in this process. Urok inase-type plasminogen activator (uPA), its receptor (uPAR), and its inhibi tor, plasminogen activator inhibitor type I (PAI-l), are proposed to be pro gnostic factors in some cancers. There are conflicting data regarding the p rognostic role of this system in endometrial cancer. Methods. To determine the prognostic value of the urokinase plasminogen act ivation system, contents of uPA, uPAR, and PAI-1 were measured in extracts of endometrial cancer tissue using ELISAs. uPA, uPAR, and PAI-1 levels were determined in 91, 54, and 92 extracts, respectively, and correlated with t umor histology, stage, grade, lymph node involvement, prevalence of metasta sis, and recurrence as well as with estrogen (ER), progesterone (PR), epide rmal growth factor (EGFR) receptor and HER-2/neu contents. Results. Patients with cancers exhibiting advanced stage, high grade, unfav orable tumor histology, nodal involvement, recurrence, and lower PR levels determined by ligand binding had significantly higher uPA content than othe rs. PAI-1 was significantly elevated in patients with advanced stage, high- grade tumor, recurrence, decreased ER content, and lower PR levels determin ed by ligand binding. uPAR did not show any relation to any of clinical and laboratory parameters. Elevated expression of PAI-1 was associated with si gnificantly shorter disease-free (P = 0.005) and overall (P = 0.0003) survi val. Multivariate analysis revealed that PAI-1 was a predictor of survival although stage was the strongest independent factor. Conclusion. Elevated uPA and PAI-I levels appear lo correlate with unfavora ble prognosis in endometrial cancer. (C) 2001 Academic Press.