Gal-GalNAc: a biomarker of colon carcinogenesis

Abstract

The disaccharide tumor marker Gal-GalNAc visualized by galactose oxidase-Schiff sequence is commonly present in cancer cells and in rectal mucus of patients with colon cancer. The expression of this marker on tissue sections taken during experimental colon carcinogenesis shows excellent correlation with human precancerous lesions and cancers. A high proportions of human precancerous lesions and even higher percentage of colon cancers express this marker, whereas, no expression is seen in the normal human large intestine. Multifocal expression of the marker is seen throughout the entire colon of patients with precancer and cancer; these include dysplasia, dilated and distorted crypts, regenerative dysplasia and hyperplastic crypts, as well as the morphologically normal crypts remote from cancer. Nearly identical pattern of Gal-GalNAc expression throughout the entire colon also appear during rat colon carcinogenesis induced by azoxzymethane including non-expression by the normal and regenerative epithelia during wound healing following mechanical injury. Thus, Gal-GalNAc detected by the simple technique of galactose oxidase-Schiff sequence, is a biomarker that appears during the very early stages of progression of carcinogenesis. The expression pattern supports the field effect theory of carcinogenesis and also explains the basis for mass screening for cancer and precancerous conditions. Chemoprevention strategy using Gal- GalNAc as an intermediate marker detected by accurate and cost-effective rectal mucus test may have great potential.