Urokinase‐type plasminogen activator, its inhibitor, and its receptor in patients with upper urinary tract carcinoma

BACKGROUND Urokinase-type plasminogen activator (uPA) is a serine protease involved in tumor invasion and metastasis. Its activity during metastasis may be regulated by a plasminogen activator inhibitor (PAI). Furthermore, uPA exerts its action by binding to a membrane-bound receptor (uPAR). The authors attempted to examine the immunohistochemical expression of uPA, uPAR, and PAI-1 in patients with transitional cell carcinoma of the upper urinary tract (TCC-UUT). METHODS Formalin fixed, paraffin embedded tumor tissues from 154 patients were analyzed using immunohistochemical staining. RESULTS There was moderate to strong cytoplasmic staining for uPA, PAI-1, and uPAR in 57.8%, 96.1%, and 88.3%, respectively, of tumor epithelial cells, and in 22.7%, 53.9%, and 24.7%, respectively, of stromal cells at the tumor/stroma interface. Examination of the relationship between immunoreactive score and clinicopathologic findings revealed that the uPA score for stromal cells significantly correlated with the stage and pattern of growth of the tumors. The PAI-1 score for tumor epithelial cells and the uPAR score for stromal cells both correlated with stage, grade, and pattern of growth. The PAI-1-score for stromal cells correlated with stage and grade. The uPAR-score for tumor epithelial cells correlated with stage. When only the immunoreactive scores that were classified as "high" (if the score was ≥ 5 or ≥ 1, for tumor epithelial and stromal cells, respectively) were considered, univariate analysis revealed that a "high" PAI-1 score for tumor epithelial cells and a "high" uPAR score for stromal cells both were significantly associated with poor disease free and overall survivals, particularly early period survival. In the final models of the multivariate analysis, only stage (all periods, disease free survival and overall survival), and grade (12 months, overall survival) were found to be progressive or prognostic factors. CONCLUSIONS Detection of immunoreactivity for plasminogen activator parameters appears to be of little or no value in determining the prognosis of patients with TCC-UUT, although some parameters were found to be associated with high stage or high grade of the tumors. Cancer 1998;82:724-32. ©; 1998 American Cancer Society.