PLASMINOGEN-ACTIVATOR INHIBITORS IN ENDOMETRIAL ADENOCARCINOMA

Background. Plasminogen activators (PA) play an important role in the mediation of pathologic processes, including cancer invasion. Levels o f urokinase are increased in malignant endometrium compared with norma l endometrium. The role of PA inhibitors (PAI) in the malignant proces s is not known. Methods. PAI-1 (endothelial type inhibitor) and PAI-2 (placental type inhibitor) in extracts of malignant (n = 14) and norma l (n = 7) postmenopausal endometrium were measured. The results were c orrelated with the standard prognostic variables in endometrial carcin oma, namely, stage, histologic grade, depth of myometrial invasion, an d estrogen receptor status of the tumor. Results. PAI-1 was not detect able in normal endometrium and was present in small quantities (0.11-1 .54 ng PAI-1/mg protein) in 4 of 14 specimens of malignant endometrium . PAI-2 was present in 4 of 7 normal and all (14 of 14) malignant endo metrial cytosols. PAI-2 levels were higher in Stage II and III compare d with Stage I cancers (P < 0.05) and in malignant endometrium that in vaded the myometrium to more than half its depth compared with those w ith less than 50% invasion (P < 0.05). No significant correlation was found between PAI-2 and estrogen receptor levels (r = 0.32). Conclusio ns. Endometrial adenocarcinoma has higher levels of PAI-2 than does no rmal postmenopausal endometrium. Highest levels of PAI-2 were found in the poorer prognostic categories of endometrial cancer.