title: Immunodetection of epithelial mucin (MUC1, MUC3) and mucin-associated glycotopes (TF, Tn, and sialosyl-Tn) in benign and malignant lesions of colonic epithelium: apolar localization corresponds to malignant transformation.
abstract: Epithelial mucins are present at the apical membranes of gastrointestinal epithelial cells or in their secretions. In this study, we examined the occurrence of peptide epitopes of the mucins MUC1 and MUC3 and of three mucin-associated glycotopes (TF, Tn, and s-Tn) in a series of colorectal tissue samples (normal colon, adenomas with different grades of dysplasia, carcinoma in situ, and invasive carcinomas). A new monoclonal antibody to a conformation-dependent peptide epitope of MUC1 was employed, which does not react with the fully glycosylated mucin as found in normal gastrointestinal mucosa. We found that adenomas acquired the ability to expose Tn, s-Tn, TF and MUC1 epitopes, and this correlated with increasing malignant potential. The secretory mucin, MUC3, revealed a different pattern: it was detectable in all sections, with maximum expression in adenomas and decrease in carcinomas. Most importantly, normal mucosa and benign lesions showed supra-nuclear and/or apical distribution of these antigens, but malignant lesions and lesions with a very high risk of malignancy revealed diffuse cytoplasmic and basolateral membrane localization. The immunohistological response to a combination of MUC1-related antibodies may assist in assessing the malignant potential and status of lesions of the colon.
authors.affiliation: Max Delbrück Centre for Molecular Medicine, Berlin-Buch, Germany.
authors.forename: Y
authors.initials: Y
authors.lastname: Cao
authors.forename: P M
authors.initials: PM
authors.lastname: Schlag
authors.forename: U
authors.initials: U
authors.lastname: Karsten
mesh_terms: D000236:Adenoma / Q000378:metabolism / Q000648:ultrastructure; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism; D002277:Carcinoma / Q000378:metabolism / Q000648:ultrastructure; D002462:Cell Membrane / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000378:metabolism; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000648:ultrastructure; D003593:Cytoplasm / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000648:ultrastructure; D007425:Intracellular Membranes / Q000378:metabolism; D018396:Mucin-1 / Q000378:metabolism*; D055263:Mucin-3; D009077:Mucins / Q000378:metabolism*; D011230:Precancerous Conditions / Q000378:metabolism
chemical_list: D015295:Antigens, Tumor-Associated, Carbohydrate; D014408:Biomarkers, Tumor; D018396:Mucin-1; D055263:Mucin-3; D009077:Mucins; C040286:Tn antigen; C055491:sialosyl-Tn antigen; C016467:Thomsen-Friedenreich antigen