Uterine fibrinolytic enzymes in endometrial cancer

Urokinase (u-PA) induced proteolysis of the extracellular matrix appears to be involved in stromal invasion by tumor cells and metastasis. Many malignant cells are known to secrete u-PA. Plasminogen activator inhibitor-type 2 (PAI-2) is an inhibitor of u-PA and is present in several neoplastic cell lines and malignant ascites. We measured u-PA and PAI-2 antigen in tissue homogenates of normal and malignant endometrium from 21 postmenopausal patients. Enzyme linked immunoassays which measure the bound and unbound, single and two chain form of the activators and bound and unbound form of the inhibitor were used. Urokinase was present in four of seven normal (range 0.15-0.5, median 0.15 ng/mg protein) and in all malignant endometrial homogenates (range 0.41-9.2, median 3.4 ng/mg protein), p < 0.001. PAI-2 was detectable in four of seven normal endometrial homogenates at low concentrations (range 1.1-3.1, median 1.1 ng/mg protein) and in all malignant tissue homogenates at higher levels (range 1.6-27.3, median 4.9 ng/mg protein), p < 0.01. Levels of PAI-2 were higher in Stage II/III compared to Stage I malignancy (p < 0.01) and in cancers that had invaded 50% or more of the uterine wall compared to less invasive cancers, p < 0.01. PAI-2 may be useful as a prognostic marker in endometrial cancer.