LOW-LEVELS OF ALPHA-L-FUCOSIDASE ACTIVITY IN COLORECTAL-CANCER ARE DUE TO DECREASED AMOUNTS OF THE ENZYMATIC PROTEIN AND ARE RELATED WITH DUKES STAGE

Colorectal cancer remains a major medical problem and survival of the patients is directly correlated to the possibility of metastases occur rence. We searched for biochemical differences between colorectal aden ocarcinomas and their precursor normal cells with the aim of complemen ting histological methods for the classification and prognosis of huma n colorectal tumours. Increased fucosylation is one of the most common phenomena associated with malignant transformation, invasion and meta stases. It might be expected that the enzyme alpha-L-fucosidase (alpha -L-fucosidase fucohydrolase E.C.3.2.1.51), involved in the breakdown o f fucose-containing glycoproteins and glycolipids, would play an impor tant role in the maintenance of the fucose content of aberrant fucosyl ated glycoconjugates. Statistical evaluation of 110 patients with colo rectal adenocarcinoma has shown that there is a significant decrease o f alpha-L-fucosidase activity in the malignant tissue compared with th e healthy colonic mucosa of the same patient. Characterisation studies have shown that there are remarkable similarities in the physicochemi cal and kinetic properties of the enzyme in both tissues. Using an imm unodetection assay we conclude that the observed decrease of alpha-L-f ucosidase activity is due to a significant decrease of alpha-L-fucosid ase protein in colorectal tumours. Our results further demonstrate tha t the alpha-L-fucosidase content (either as enzymatic activity or as e nzymatic protein) is lower in primary tumours at advanced stages (Duke s' B and C) than in primaries at early stages (Dukes' A).