Prognostic Value of Urokinase Plasminogen Activator and Plasminogen Activator Inhibitor-1 in Renal Cell Cancer

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Abstract
Urokinase type plasminogen activator and its inhibitor plasminogen activator inhibitor are associated with invasion and formation of metastases in tumors. In a prospective study urokinase and plasminogen activator inhibitor-1 content in renal cell cancer and benign renal tissue was correlated with the traditional prognostic factors of TNM staging and grading as well as ploidy and actual clinical outcome of the patients. A total of 152 patients, who underwent transperitoneal tumor nephrectomy for renal cell cancer, was followed for a mean of 23.9 months. Urokinase and plasminogen activator inhibitor-1 from the tumor tissue and corresponding benign renal tissue were quantified from detergent extracted tissue samples (1 percent triton-X-100 in TBS) and measured with an enzyme-linked immunosorbent assay. Urokinase content correlated with the development of distant metastases (log rank 4.32, p = 0.037). Cutoff value was 0.84 ng./mg. A group of 11 patients were considered to be at high risk for metastases (9 events) based on urokinase greater than 0.84 ng./mg., while 94 patients were considered to be at low risk (5 events) with urokinase less than 0.84 ng./mg. Plasminogen activator inhibitor-1 significantly correlated with the prevalence of distant metastases (log rank 5.17, MO, 10.04 versus M1, 23.79, p = 0.02) and the development of new metastases postoperatively (M0, 10.85 versus M1, 27.36, p = 0.001). Cutoff value was 12 ng./mg. protein. A group of 41 patients were considered at high risk for relapse (6) based on plasminogen activator inhibitor-1 greater than 12 ng./mg. protein compared to 55 patients with plasminogen activator inhibitor-1 less than 12 ng./mg. protein with only 1 relapse during followup. Plasminogen activator inhibitor-1, the specific inhibitor of urokinase is a strong and independent prognostic factor in predicting early relapse of renal cell carcinoma. High and low risk groups for disease-free survival can be discriminated by plasminogen activator inhibitor-1 antigen content in the tumor tissue.