Ectopic expression of the Y (Ley) antigen defined by monoclonal antibody 12-4LE in distal colonic adenocarcinomas

Abstract

Monoclonal antibody (MAb) 12-4LE reacts specifically with the alpha Fuc(1-2) beta Gal(1-4) [alpha Fuc(1-3)]GlcNAc-R synthetic oligosaccharide and consequently characterizes the Y (Ley) antigen. In normal individuals, this MAb reacts more strongly on samples from blood group O persons, indicating that the Y structure is better recognized when terminal A or B sugars are not added to the Y structure. In fetal and normal adult gastrointestinal tract, this antibody reacts with the epithelium of stomach, small intestine and proximal colon, but not of distal colon. In the adult, cells from the surface epithelium of the gastric, small intestinal and cecal mucosae express the Y antigen according to the secretor phenotype of each individual, thus characterizing the so-called "upward differentiation" pattern. In contrast, mucus cells of the pylorus and duodenal Brünner glands, as well as Paneth cells, always express the Y antigen irrespective of secretor phenotype, thereby characterizing the so-called "downward differentiation" pattern. Proximal fetal colonic mucosa has the same genetic control as the downward differentiation pattern of the adult. Distal fetal colonic mucosa is negative with anti-Y, as in the adult. Y antigen was not expressed in hyperplastic (10 cases), juvenile (5 cases) or adenomatous (43 cases) polyps, except for some spreading villous adenomas in which rare Y-positive foci could be observed but which were not specifically associated with dysplastic glands. Polyps from familiar polyposis did not express this antigen. In adenocarcinomas, the Y antigen was expressed in 41/45 (91%) of distal tumors and 15/35 (43%) of cecal tumors, independently of ABO phenotype. The ectopic expression of this Y antigen on distal colon adenocarcinomas may be a useful tool in the detection of distal colonic carcinomas.