A prospective study on the prognostic significance of urokinase-type plasminogen activator levels in breast cancer tissue

• Published in: Journal of cancer research and clinical oncology 1997, Vol.123 (10), p.555-559
• Main Authors: SHIBA, E, SEUNG JIN KIM, TAKAI, S.-I, TAGUCHI, T, IZUKURA, M, KOBAYASHI, T, FURUKAWA, J, YAYOI, E, SHIN, E, TAKATSUKA, Y, KOYAMA, H
• Format: Article
• Language: English
• Subjects: Age Factors; Biological and medical sciences; Breast Neoplasms - enzymology; Cytosol - enzymology; Disease-Free Survival; Enzyme-Linked Immunosorbent Assay; Female; Gynecology. Andrology. Obstetrics; Humans; Lymphatic Metastasis; Mammary gland diseases; Medical sciences; Multivariate Analysis; Neoplasm Recurrence, Local - epidemiology; Prognosis; Prospective Studies; Receptors, Estrogen - metabolism; Receptors, Progesterone - metabolism; Regression Analysis; Risk; Survival Analysis; Tumors; Urokinase-Type Plasminogen Activator - metabolism
• ISSN: 0171-5216; 1432-1335
• DOI: 10.1007/s004320050104

Urokinase-type plasminogen activator (u-PA), which cleaves plasminogen to yield plasmin, is a serine protease of fibrinolysis and is presumed to play a key role in extracellular proteolysis and facilitate the migration of cancer cells. This study was conducted prospectively to evaluate the prognostic significance of u-PA antigen level in breast cancer tissues. u-PA concentrations in the cytosol of 226 breast cancer tissues were determined prospectively by enzyme-linked immunosorbent assay using cytosol fractions prepared for steroid hormone assay. The median follow-up period of the patients was 60 months. Various prognostic factors were evaluated by univariate analysis or multivariate analysis using the Cox proportional-hazards method. Patients with primary breast cancer containing high levels of u-PA had a significantly shorter disease-free survival than patients with low levels of u-PA antigens. In multivariate analysis, a high level of u-PA was an independent risk factor for disease-free survival, being independent of age, axillary node status, and estrogen receptor status. Among the major prognostic factors, a high u-PA antigen level, lymph node involvement, and a positive estrogen receptor status were the most important for predicting relapse-free survival (P = 0.044, P < 0.0001, P = 0.0039). This first prospective study confirmed the prognostic significance of the u-PA antigen level in association with other major prognostic factors. The results of our present study suggest that u-PA in breast cancer tissue might be involved in breast cancer invasion and metastasis.