The complex between urokinase and its type-1 inhibitor in primary breast cancer: Relation to survival

We examined the relationship between tumor tissue level of the complex form ed of urokinase (uPA) and its type-1 inhibitor (PAI-1) and survival of brea st cancer patients. The study included 342 axillary lymph node negative and -positive primary breast cancer patients with a median follow-up of 67 mon ths. Using a newly established ELISA, the levels of preformed uPA PAI-1 com plex were measured in tumor tissue extracts and analyzed with respect to to tal uPA, total PAI-1, and clinicopathological parameters, including surviva l. uPA PAI-1 complex comprised a minor, variable fraction of both total uPA and PAI-1 levels. The complex levels were higher in node-negative tumors t han in node-positive tumors and higher in small and low-grade tumors (all, P less than or equal to 0.002). The tumor levels of complex, uPA, and PAI-1 were all associated with survival; high complex levels predicted longer re currence-free survival (P = 0.03) and overall survival [OS (P = 0.005)], wh ereas high uPA or PAI-1 levels significantly predicted shorter survival. In multivariate Cox analysis, the only parameters that independently predicte d survival were total PAI-1 level and lymph node status for recurrence-free survival and OS and, additionally, steroid hormone receptor status and gra de for OS. This is the first demonstration of a relationship between uPA PA I-1 complex tumor Level and patient survival. However, total PAI-1 level sh owed superior prognostic power. Additional studies are needed to understand the relationship of these parameters to cancer biology and to assess the c linical utility of the uPA PAI-1 complex.