Urokinase-type plasminogen activator (u-PA) antigen is a predictor of early relapse in breast cancer

Abstract

Cancer tissue contains elevated levels of the urokinase-type plasminogen activator (u-PA). Experimental evidence supports the assumption that u-PA is related to invasion and metastasis. The aim of this study was to determine whether the u-PA content of human breast cancer tissue is a prognosis-associated factor. Tissue samples from breast cancer patients were assessed for u-PA antigen by ELISA and immunohistochemistry applying monoclonal antibodies. u-PA in breast cancer tissue was localised in the cytoplasm and plasma membrane of tumour cells. u-PA was quantitated in detergent-extracted tissue samples (1% Triton X-100 in TBS) obtained from patients with breast cancer (n =115) and benign lesions (n = 30). Median values of 2.62 ng versus 0.23 ng u-PA/mg protein were determined. Patients with high u-PA content (u-PA > 2.6 ng/mg protein) already showed a statistically significant higher incidence of relapse compared to patients with low u-PA content (26% versus 2%) after a median follow-up of 12.5 months (range 2–26 months). Multivariate regression analysis revealed that compared with established prognostic factors, u-PA had the strongest impact on relapse rate (relative risk RR=21.1), followed by hormone receptor status (RR = 5.8) and lymph node involvement (RR = 3.0). We conclude that the u-PA content of breast cancer tissue is an independent prognostic factor in predicting early relapse. High or low risk patients can be selected by u-PA determination within the stated risk groups defined by locoregional extension and hormone receptor status.