PLASMINOGEN-ACTIVATOR INHIBITOR TYPE-2 IN BREAST-CANCER

The serine protease urokinase plasminogen activator (uPA) is causally involved in cancer invasion and metastasis. Activity of this protease in vivo is controlled principally by two inhibitors, one of which is p lasminogen activator inhibitor type 2 (PAI-2). In this study, we show that PAI-2 levels were significantly higher in primary breast carcinom as (n = 152) than benign breast tumours (n = 18). In the primary cance rs, PAI-2 levels correlated weakly but significantly with those of uPA and PAI-1, but not with tissue type plasminogen activator (tPA) or uP A receptor (uPAR) levels. Using Northern blotting, mRNA for PAI-2 was found in 28.6% of 49 primary breast cancers. In contrast to findings a t the protein level, PAI-2 mRNA levels failed to correlate with those for uPA or PAI-1. After immunocytochemistry with primary cancers, PAI- 2 was detected predominantly in the malignant cells of primary carcino mas but was also present in stromal cells. Using the median value as a cut-off point, PAI-2 showed no significant relationship with either d isease-free interval or overall survival. However, using an optimum cu t-off value, patients with low levels of PAI-2 had a worse outcome tha n those with a high level. We conclude that, unlike PAI-1, high levels of PAI-2 may be a favourable prognostic marker in breast cancer.