The urokinase plasminogen activator system as a target for prognostic studies in breast cancer

The identification of patients at high risk of relapse is currently one of the most important issues in breast cancer research. However, the selection of high-risk patients continues to be difficult due to the unpredictable c ourse of this disease. Axillary lymph node status is currently recognized a s the best clinical discriminant between good and poor prognosis, yet almos t 30% of node-negative patients and 65% of node-positive patients will expe rience a relapse. Additional prognostic markers are therefore urgently need ed. Since metastatic disease is the main cause of cancer patient morbidity and mortality, the measurement of molecules functionally involved in the regula tion of tumor invasion and metastasis is attractive as a means to predict p rognosis. Cancer invasion is a complex process in which degradation of the extracellu lar matrix plays a crucial role. This degradation is accomplished by the co ncerted action of several proteolytic enzyme systems, including generation of plasmin by the urokinase pathway of plasminogen activation, matrix metal loproteases, and other extracellular proteases. Increased expression and se cretion of urokinase plasminogen activator (uPA) strongly correlates with t he malignant phenotype of many types of-cells, and the central role of uPA in tumor invasion is now well established. This review will focus on the prognostic impact of components of the urokin ase plasminogen activation system in breast cancer with emphasize on method ological issues.