Serine proteases convert plasminogen to plasmin which is involved in tissue remodeling under physiologic and pathophysiologic conditions, including breast carcinoma invasion and progression. Both urokinase-type plasminogen activator (uPA) and pro-uPA associate with uPA receptor (uPAR) on target cells, where plasminogen activator inhibitors (e.g., PAI-1) may modulate their activities. Expression levels of these factors were compared in breast carcinomas relative to patient characteristics, carcinoma features, and clinical outcome. uPA, uPAR, and PAI-1 were quantified by enzyme-linked immunosorbent assay (ELISA) in extracts of 226 biopsies while estrogen receptor (ER) and progestin receptor (PR) were determined by enzyme immunoassay (EIA) or radio-ligand binding. Each set of assays contained a novel reference specimen with known quantities of each of these five analytes. Levels in ng/mg protein of these biomarkers exhibited ranges: uPA (0-12.3); uPAR (0-19.5); PAI-1 (0-91.2). When considered independently, expression of uPA, uPAR, or PAI-1 was unrelated to patient age or menopausal status. Although no correlation was observed between each analyte with stage, grade, or ER/PR status, levels appeared to differ with pathology and nodal status. A dendrogram from hierarchical clustering of uPA, uPAR, and PAI-1 levels in 106 specimens revealed three clusters of breast cancer patients. Kaplan-Meier analyses of uPA, uPAR, and PAI-1 indicated a correlation with overall survival (OS), suggesting collective examination of these biomarkers is useful in predicting clinical outcome of breast cancer.
© 2012 Wiley-Liss, Inc.