PLASMINOGEN-ACTIVATOR INHIBITOR-2 - PROGNOSTIC RELEVANCE IN 1012 PATIENTS WITH PRIMARY BREAST-CANCER

The antigen levels of urokinase-type plasminogen activator (uPA) and i ts inhibitor plasminogen activator inhibitor (PAI) 1, as detected in t umor extracts by ELISA, have been reported to be correlated with a poo r prognosis in primary breast cancer. In the present study we have cha racterized a novel PAI-2-specific ELISA, designed to measure PAI-2 ant igen levels in tumor cytosols. We determined PAI-2 antigen levels alon g with those of uPA and PAI-1 in 1012 routinely prepared tumor cytosol s of patients with primary breast canter (median follow-up, 71 months) . In the overall population there was no significant association betwe en the level of PAI-2 and prognosis, while in tumors with high uPA val ues, PAI-2 (test for trend) was associated with a prolonged relapse-fr ee survival, metastasis-free survival, and overall survival (for all a nalyses, P < 0.02). In Cox's multivariate analysis for relapse-free su rvival, metastasis-free survival, and overall survival in tumors with high uPA values (including patient's age, menopausal status, lymph nod e status, tumor size, estrogen and progesterone receptor status, uPA, and PAI-1), PAI-2 either dichotomized or, as a continuous variable, wa s independently associated with a favorable relapse-free survival, met astasis-free survival, and overall survival. We conclude that the PAI- 2-specific ELISA described herein is well suited for the measurement o f PAI-2 levels in cytosols routinely prepared for analysis of steroid hormone receptors. We speculate that PAI-2 may serve as an inhibitor f or uPA in human primary breast cancers.