Plasminogen activator inhibitors in endometrial adenocarcinoma

Abstract

Plasminogen activators (PA) play an important role in the mediation of pathologic processes, including cancer invasion. Levels of urokinase are increased in malignant endometrium compared with normal endometrium. The role of PA inhibitors (PAI) in the malignant process is not known. PAI-1 (endothelial type inhibitor) and PAI-2 (placental type inhibitor) in extracts of malignant (n = 14) and normal (n = 7) postmenopausal endometrium were measured. The results were correlated with the standard prognostic variables in endometrial carcinoma, namely, stage, histologic grade, depth of myometrial invasion, and estrogen receptor status of the tumor. PAI-1 was not detectable in normal endometrium and was present in small quantitities (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 endometrial cytosols. PAI-2 levels were higher in Stage II and III compared with Stage I cancers (P < 0.05) and in malignant endometrium that invaded the myometrium to more than half its depth compared with those with less than 50% invasion (P < 0.05). No significant correlation was found between PAI-2 and estrogen receptor levels (r = -0.32). Endometrial adenocarcinoma has higher levels of PAI-2 than does normal postmenopausal endometrium. Highest levels of PAI-2 were found in the poorer prognostic categories of endometrial cancer.