Distribution of sialosyl Tn and Tn antigens within normal and malignant colorectal epithelium

Abstract

Expression of the core blood group structures sialosyl Tn (STn) and Tn is regarded as a colorectal cancer-specific change reflecting truncated synthesis of the oligosaccharide component of goblet cell mucin. The distribution of STn and Tn in normal and malignant epithelium has been studied in detail by a combination of mucin-, lectin-, and immunohistochemistry with and without pretreatment with potassium hydroxide (KOH), neuraminidase, and KOH-neuraminidase. When O-acetylated sialic acid (neuraminidase-resistant) is converted by saponification to non-O-acetylated sialic acid (neuraminidase-sensitive), normal colorectal goblet cells (mainly of the lower two-thirds of crypts) are immunoreactive with the monoclonal antibody TKH2 (specific for STn). This immunoreactivity is abolished by the interposition of neuraminidase, but goblet cells then become immunoreactive with Hb-Tn1 (specific for Tn). While colorectal cancer mucin expresses STn, expression of Tn is not seen in either goblet cell mucin or extracellular material showing the morphological and histochemical characteristics of secretory mucin. Tn expression in cancers is mainly limited to the Golgi zone and in a proportion of cases to cytoplasm and apical membrane (glycocalyx) of columnar cells and inspissated material within lumina. The material reacting with Hb-Tn1 may be upregulated, membrane-associated MUC1 glycoprotein rather than MUC2 or MUC4 goblet cell mucin. The presence of STn and cryptic Tn within normal colorectal goblet cells and the absence of Tn expression within colorectal cancer secretory mucin contradicts the generally accepted concept of cancer-specific incomplete glycoprotein synthesis within these neoplasms.