Prognostic impact of stromal cell-derived urokinase-type plasminogen activator in gastric carcinoma

BACKGROUND: Urokinase-type plasminogen activator (uPA) plays an important role in the destruction of the extracellular matrix and basement membrane around cancer cells. In the current study, the authors investigated uPA expression in cancer cells and stromal cells in patients with gastric carcinoma. METHODS: uPA activity was determined by an enzymatic assay using synthetic substrate (S-2444) in tumor specimens obtained from 71 patients with gastric carcinoma and was compared with the results of immunohistochemical staining for uPA. RESULTS: Higher uPA activity was significantly associated with tumors with peritoneal metastases and tumors with deeper invasion into the gastric wall. Undifferentiated tumors showed significantly higher uPA activities compared with differentiated tumors. The 25 patients with high uPA activity (> or = 60 U/mg protein) had a lower survival rate than the 46 patients with low uPA activity (< 60 U/mg protein) (P < 0.05). uPA activity showed prognostic significance in patients with International Union Against Cancer Stage II and Stage III tumors (P < 0.05, respectively). There was no significant relation between immunohistochemical expression of uPA in cancer cells and uPA enzymatic activity. However, uPA expression in stromal cells significantly correlated with uPA activity in tumor tissues. The uPA expression in stromal cells also correlated with tumor histology and peritoneal metastases. CONCLUSIONS: These results suggest that uPA enzymatic activity is a prognostic factor in gastric carcinoma, and that uPA produced by stromal cells may regulate cancer cell invasion.