HIGH-LEVEL OF UROKINASE-TYPE PLASMINOGEN-ACTIVATOR IS A NEW PROGNOSTIC MARKER IN PATIENTS WITH GASTRIC-CARCINOMA

BACKGROUND. Prognosis of gastric carcinoma is related to invasion and metastasis. Evidence has accumulated that invasion and metastasis in s olid tumors require the action of tumor-associated proteases, which pr omote the dissolution of the surrounding tumor matrix and the basement membrane. The serine protease protease urokinase-type plasminogen act ivator (uPA) and its inhibitor, plasminogen activator inhibitor-1 (PAI -1), appear to have a major function in these processes. Recent report s have demonstrated that expression of these proteolytic enzymes is el evated in breast and colon carcinoma and that it can be associated wit h invasiveness and poor prognosis. Therefore, the authors evaluated wh ether tile expression and activation of uPA and PAI-1 might be of clin ical value as a tumor/biologically defined risk factor in patients wit h gastric carcinoma. METHODS. Enzyme-linked immunoadsorbent assays wer e used to test for uPA antigens and PAI-1 in tissue extracts of normal and cancerous tissue from 160 gastric carcinoma patients who were enr olled in the Yonsei Cancer Center Study Group. RESULTS. Both uPA and P AI-1 levels were significantly higher in cancerous tissues than in nor mal tissues (uPA: 9.4 +/- 8.7 vs. 5.3 +/- 3.1 ng/mg protein cytosol; P AI-1: 10.9 +/- 9.1 vs. 5.8 +/- 2.9 ng/mg protein cytosol), (P < 0.001, respectively). Both high uPA and PAI-1 levels were associated with di fferentiation of the tumor (P = 0.04 and P = 0.004, respectively), and a high PAI-1 level was associated with lymph node metastasis at an ad vanced stage (P = 0.003 and P = 0.04, respectively). There was a corre lation between the levels of uPA and PAI-1 expression in cancerous tis sues (correlation coefficient = 0.57). In univariate analysis, a high level of uPA or PAI-1 was associated with a short relapse free surviva l, but in multivariate analysis only a high level of uPA was an indepe ndent prognostic parameter for a short relapse free survival for gastr ic carcinoma patients. CONCLUSIONS. These data indicate that uPA is a new independent variable for the identification of high risk gastric c arcinoma patients. Therefore, therapy targeting uPA can be applied as a ne iv biologic treatment modality for these individuals. (C) 1997 Am erican Cancer Society.