Proteases in gastrointestinal neoplastic diseases

Cysteine and serine proteases are involved in cancer invasion and metastasi s. In the past few years we investigated the tissue levels of these proteas es in gastric cancer (GC), gastric precancerous changes (CAG), colorectal c ancer (CRC) and the plasma and serum levels of proteases in several gastroi ntestinal rumours. using ELISA methods. Significantly higher antigen levels were found not only in GC tissue but also in CAG with respect to the level s found normal tissue; with respect to GAG, patients with dysplasia had hig her levels than patients without dysplasia. The same findings were obtained in CRC. In general protease levels correlated with the major histomorpholo gical parameters, such as grading and histotype in GC as well as in CRC. Ti ssue protease levels had a strong prognostic impact in GC, in which UPA was singled out by multivariate analysis as the major prognostic factor, and C RC. The plasma levels of urokinase-type plasminogen activator (UPA) and the serum levels of cathepsin B were significantly increased in patients with gastrointestinal tumours. In conclusions, cysteine and serine proteases may have a part not only in GC and CRC invasion and metastasis, but also in th e progression of gastric precancerous changes into cancer. They are strong prognostic factors in GC and CRC. These proteases may also have a role as t umour markers in the early diagnosis of gastrointestinal tract rumours. (C) 2000 Elsevier Science B.V. All rights reserved.