Prognostic impact of urokinase-type plasminogen activator (uPA) and its inhibitor (PAI-1) in cytosols and pellet extracts derived from 892 breast cancer patients

To evaluate the clinical relevance of urokinase-type plasminogen activator (uPA) and its type-1 inhibitor (PAI-1) measured by a recently developed enz yme-linked immunosorbent assay (ELISA), we analysed both components in samp les derived from 892 patients with primary breast cancer (median follow-up 99 months). The assays were performed in cytosolic extracts as well as in c orresponding detergent extracts of pellets obtained after ultracentrifugati on, which was carried out when preparing the cytosolic fractions for routin e steroid hormone receptor determination. Statistically significant correla tions were found between the cytosolic levels and those determined in the p ellet extracts (Spearman correlation coefficient r(s) = 0.60, P< 0.0001 for uPA and r(s) = 0.65, P< 0.0001 for PAI-1). Furthermore, strong correlation s were found between the levels of both uPA (r(s) = 0,85, P< 0.0001) and PA I-1 (r(s) = 0.90, P< 0.0001) in the cytosols and their levels previously me asured with ELISAs based on commercial reagents. in both Cox univariate and multivariate analysis, high cytosolic levels of uPA or PAI-1 were signific antly associated with increased rates of relapse and death. The levels of u PA and PAI-1 in the pellet extracts also provided prognostic information, a lthough to a lesser extent compared with the cytosolic extracts, The predic tion of prognosis on the basis of uPA and PAI-1 assessed by an alternative ELISA once again emphasizes the established prognostic role and usefulness of these parameters in selection of breast cancer patients at high or low r isk of recurrence.