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Topics {✒️}

nadia harbeck md kurt ulm phd node-negative breast cancer short-term organ culture month download article/chapter urokinase-type plasminogen activator tissue-type plasminogen activators lothar pache md node-negative patients early breast cancer privacy choices/manage cookies human breast cancer manfred schmitt phd urokinase plasminogen activator urokinase-plasminogen activator lymph node status human plasminogen activator breast cancer patients primary breast cancer aggressive breast carcinomas plasminogen activator content human ovarian carcinoma metastatic colon tumors wilhelm sander-stiftung proportional hazard model full article pdf de la garza human a431 cells human granulocytes stimulated paraffin-embedded tissue plasminogen activator secretion european economic area 97 ng/mg protein 18 ng/mg protein kluwer academic publishers fibrin-fibronectin compounds tumor tissue extracts estrogen receptor assays independent prognostic factor conditions privacy policy gastric tumor explants human colonic tumors stroma-derived fibrin tumor cell prourokinase independent prognostic factors cox regression model pro-urokinase receptors surrounding tumor matrix accepting optional cookies enzyme-linked immunoassays

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         headline:Urokinase (uPA) and its inhibitor PAI-1 are strong and independent prognostic factors in node-negative breast cancer
         description:Evidence has accumulated that invasion and metastasis in solid tumors require the action of tumor-associated proteases, which promote the dissolution of the surrounding tumor matrix and the basement membranes. The serine protease urokinase-type plasminogen activator (uPA), which is elevated in solid tumors, appears to play a key role in these processes. We used enzyme-linked immunoassays (ELISA) to test for uPA antigen and its inhibitor PAI-1 in tumor tissue extracts of 247 breast cancer patients who were enrolled in a prospective study. The relation of these data to known prognostic factors and to other variables such as DNA analysis and cathepsin D was studied. Disease-free and overall survival were analyzed according to Cox's proportional hazard model. The major new finding is that breast cancer patients with either high uPA (>2.97 ng/mg protein) or high content of the uPA inhibitor PAI-1 (>2.18 ng/mg protein) in their primary tumors have an increased risk of relapse and death. Multivariate analyses revealed uPA to be an independent and strong prognostic factor. The impact of uPA is as high as that of the lymph node status. In node-negative patients the impact of uPA is closely followed by that of PAI-1. Since uPA and PAI-1 are independent prognostic factors, the node-negative patients could be subdivided further by combining these two variables. In this refined analysis, patients whose primary tumors have lower levels of both antigens evidently have a very low risk of relapse (93% disease-free survival at three years) in contrast to patients with high uPA and high PAI-1 (55% disease-free survival at three years). The combination of uPA and PAI-1 in our group of patients with axillary node-negative breast cancer allows us to identify the 45 percent of patients having an increased risk of relapse. Consequently, more than half of the patients had less than a 10% probability of relapse and thus would possibly be candidates for being spared the necessity of adjuvant therapy.
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