Blood group-related carbohydrate antigen expression in malignant and premalignant colonic neoplasms

Abstract

Cell surface glycoconjugates of colonic epithelial cells carry certain carbohydrate antigens related to blood group substances. During the progression to malignancy, these oligosaccharide immunodeterminants undergo specific types of alterations. In colon cancers, the blood group antigens A, B, H, and Le(b), which are normally expressed only in the proximal colon, can be re-expressed in distal colon cancers or deleted in proximal colon cancers. Also, an antigen which is incompatible with the individual's blood type can be expressed. Similar alterations occur in adenomatous polyps, but with reduced frequency. The simple form of blood group-related Le(x) and Le(y) antigens found in normal mucosa can undergo modification by oligosaccharide elongation, internal fucosylation, and sialylation into novel structures found in carcinomas as well as in adenomas with greatest malignant potential. Finally, antigens representing the first steps of glycosylation, Tn, T, sialosyl-Tn (STn), which are normally cryptic in the colon, can be unmasked due to incomplete glycosylation in adenomatous polyps and cancers. Several of these antigens, such as extended Le(x), extended Le(y), T, and sialosyl-Tn, are quite cancer-specific in that they are rarely expressed in normal mucosa or hyperplastic polyps, but preferentially occur in adenomas of greatest malignant potential. As such, these antigens might be useful as candidate intermediate endpoint biomarkers.