INCREASED LEVELS OF CATHEPSIN-B AND CATHEPSIN-L, UROKINASE-TYPE PLASMINOGEN-ACTIVATOR AND ITS INHIBITOR TYPE-1 AS AN EARLY EVENT IN GASTRICCARCINOGENESIS

Background: Cysteine proteases [cathepsin B (CATB), cathepsin L (CATL) ], the serine protease urokinase-type plasminogen activator (UPA) and its inhibitor type-1 (PAI-1) play an important part in cancer invasion . No data are available on the relationship between these proteases an d gastric precancerous changes, Aims: To determine CATB, CATL, UPA, PA I-1 in chronic atrophic gastritis, intestinal metaplasia and gastric e pithelial dysplasia, as precancerous changes, and to compare these dat a with those obtained in gastric cancer, Patients: Endoscopic biopsies were obtained from 12 patients with gastric cancer (cancerous tissue) , 33 patients with chronic atrophic gastritis (all with intestinal met aplasia and 12 with dysplasia) and from 47 control subjects, for a tot al of 92 patients, Methods: Antigen concentrations were measured using ELISA methods, Immunohistochemistry was performed using monoclonal an ti-CATB and anti-PAI-1 antibodies, Results: CATB, CATL, UPA and PAI-1 were significantly higher in chronic atrophic gastritis than in contro ls (CATB: P < 0.001; CATL: P < 0.005; UPA: P < 0.000001; PAI-1: P < 0. 005), The same was observed for cancer, CATB and UPA were significantl y higher in chronic atrophic gastritis, with versus without dysplasia (P < 0.05), Dysplastic epithelia showed strong immunoreactivity to PAI -1 and CATB, Conclusions: Our study demonstrates that cathepsins, UPA and PAI-1 may have a role not only in the process of cancer invasion, but also in the progression of precancerous changes into cancer.