Expression of large intestinal mucin antigen (LIMA) epitopes in the normal and neoplastic gastrointestinal tract.
This study has identified the expression in normal and neoplastic gastrointestinal (GI) tract of epitopes on the colonic mucin LIMA (large intestinal mucin antigen), which are unique markers of normal colonic differentiation. Six anti-LIMA monoclonal antibodies (MAbs) (22D4, 9B5, 2C3, 23B2, 46A2, and 10B3) were studied immunohistochemically in normal GI tract, colorectal adenomas, and colorectal and gastric cancers. All MAbs showed specificities consistent with distinct epitopes, five of which were neuraminidase-resistant and four periodate-sensitive. Each reacted with mucin in 60-100 per cent normal colons--MAbs 10B3 and 23B2 also with small intestinal mucin--but none with gastric mucin. Five MAbs showed crypt and regional gradients in normal colon, MAbs, 22D4, 9B5, and 2C3 showing a hierarchy of reactivities in the crypt. Individual adenomas showed decreasing goblet cell (GC) LIMA expression with increasing size. However, 30 per cent of familial adenomatous polyposis (FAP) patients had generalized background losses of 9B5 and 2C3 GC reactivity, retaining 22D4, whilst 44 per cent of non-FAP patients lost 22D4 GC reactivity, regaining 9B5 and 2C3--evidence for polymorphism of mucin expression. All colorectal cancers expressed LIMA epitopes (frequently weaker than normal), and three MAbs (22D4, 9B5, and 2C3) showed deeper than normal staining in adjacent crypts. Eighty-five per cent of gastric cancers also expressed LIMA epitopes.
Pilbrow
S J
SJ
Biochemistry Department, Monash University, Clayton, Victoria, Australia.
Hertzog
P J
PJ
Pinczower
G D
GD
Linnane
A W
AW
D000236:Adenoma / Q000276:immunology; D011125:Adenomatous Polyposis Coli / Q000276:immunology; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000276:immunology; D015415:Biomarkers / Q000032:analysis; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002454:Cell Differentiation; D003106:Colon / Q000276:immunology; D004064:Digestive System / Q000276:immunology; D000939:Epitopes / Q000032:analysis*; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000276:immunology*; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D009077:Mucins / Q000276:immunology*; D013274:Stomach Neoplasms / Q000378:metabolism
D000911:Antibodies, Monoclonal; D015415:Biomarkers; D014408:Biomarkers, Tumor; D000939:Epitopes; D009077:Mucins