STRONG PROGNOSTIC IMPACT OF TUMOR-ASSOCIATED UROKINASE-TYPE PLASMINOGEN-ACTIVATOR IN COMPLETELY RESECTED ADENOCARCINOMA OF THE ESOPHAGUS

The serine protease system has been shown to play an important role in the invasive potential of a variety of tumors. To date, however, ther e are little data about the expression of these proteases in esophagea l carcinoma. To determine the level of expression and the significance of urokinase-type plasminogen activator (uPA) and its plasminogen act ivator inhibitor type 1 (PAI-1) in adenocarcinoma of the esophagus, we studied 54 tumor cases and a control group of normal gastric mucosa c ases with ELISA using detergent-extracted samples. uPA and PAI-1 were significantly elevated as compared to control tissue by factors of 16 and 14, respectively. Median levels of both uPA and PAI-1 showed signi ficant correlation with tumor pT, pN, and pM categories, whereas the p resence of lymphatic invasion correlated only with the uPA content and tumor grade correlated only with PAI-1 content. Using maximally selec ted statistics, a cutoff value was found for uPA (21.85 ng/mg protein) but not for PAI-1, which divided the study group into significantly p oorer and better survival subgroups. By univariate analysis, depth of tumor invasion (pT), lymph node involvement (pN), number of involved l ymph nodes, lymph node ratio, distant nodal metastases [pM(1(lym))], l ymphatic invasion, and uPA showed significant correlations with patien t survival. By multivariate analysis, uPA (first rank), pN, and pM (ly m) were identified as independent prognostic factors, with relative ri sks of 8.4, 4.1, and 4.3, respectively. In a second survival analysis method, a prognostic model was developed using classification and regr ession trees analysis, in which a significant difference among three p atient survival groups was distinguished using the variables ''number of involved lymph nodes'' and ''uPA content.'' In summary, tumor uPA c ontent as determined by ELISA appears to be a powerful, independent pr ognostic factor for survival in adenocarcinoma of the esophagus.