Colonic mucin-carbohydrate components in colorectal tumors and their possible relationship to MUC2, p53 and DCC immunoreactivities.
To clarify changes in mucus components during colorectal tumorigenesis, we developed novel monoclonal antibodies (Abs) against carbohydrate chains of human colorectal mucin (HCM) obtained from normal sigmoid and rectal mucosae. A hundred and ninety-nine cases of colorectal carcinoma and 67 cases of tubular adenoma, along with 250 normal colonic tissue samples, were investigated immunohistochemically. The results were compared with clinical stage, survival and MUC2 (core protein of the intestinal type mucin) expression, as well as with the status of the p53 and DCC (deleted in colorectal carcinomas) genes. In the normal colonic epithelium, HCM14 Ab reacted with the cytoplasmic regions of the goblet cells and enterocytes, while HCM21 Ab bound to mucous droplets in the former, suggesting a more mature carbohydrate structure. Both HCM14 and 21 scores were significantly decreased in adenomas and carcinomas. This is in line with an altered PAS-Alcian blue staining, indicating accumulation of mucins with incomplete or abnormal glycosylation in tumors. Levels of HCM14 and 21 binding tended to show a positive correlation with expression of MUC2 and DCC, and a negative association with p53 protein accumulation in carcinomas, although there was no apparent link to Duke's stage or the prognostic outcome. These findings suggest a possible involvement of alterations in mucin carbohydrate in colorectal tumor development. The observed changes may be associated with loss of MUC2 and DCC expression, as well as with p53 protein accumulation.
Hara
A
A
Department of Pathology, Kitasato University School of Medicine, Kanagawa, Japan.
Saegusa
M
M
Mitomi
H
H
Kurihara
M
M
Ishihara
K
K
Hotta
K
K
Okayasu
I
I
D000230:Adenocarcinoma / Q000737:chemistry* / Q000473:pathology; D000236:Adenoma / Q000737:chemistry* / Q000473:pathology; D000818:Animals; D000911:Antibodies, Monoclonal; D000918:Antibody Specificity; D014408:Biomarkers, Tumor / Q000032:analysis; D015815:Cell Adhesion Molecules / Q000032:analysis*; D003106:Colon / Q000737:chemistry; D015179:Colorectal Neoplasms / Q000737:chemistry* / Q000473:pathology; D000075389:DCC Receptor; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D051379:Mice; D008807:Mice, Inbred BALB C; D055262:Mucin-2; D009077:Mucins / Q000032:analysis*; D009363:Neoplasm Proteins / Q000032:analysis; D011956:Receptors, Cell Surface; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*; D025521:Tumor Suppressor Proteins
D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; D015815:Cell Adhesion Molecules; D000075389:DCC Receptor; C501909:DCC protein, human; C501910:Dcc protein, mouse; C524625:MUC2 protein, human; C524626:Muc2 protein, mouse; D055262:Mucin-2; D009077:Mucins; D009363:Neoplasm Proteins; D011956:Receptors, Cell Surface; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins