Monoclonal antibody TKH2 to the cancer-associated epitope sialosyl Tn shows cross-reactivity with variants of normal colorectal goblet cell mucin.
It has been suggested that synthesis of mucin-type carbohydrate chains may be arrested at the core structure Tn. This may occur following premature sialylation of Tn giving the structure STn. TKH2, a monoclonal antibody to STn, is regarded as showing highly specific reactivity with colorectal and other epithelial neoplasms. In this study we have shown that TKH2 cross-reacts with normal colorectal goblet cells that are mild PAS positive (specific for non-O-acetylated sialic acid). Approximately 9% of caucasians secrete colorectal mucin in which sialic acid is non-O-acetylated. TKH2 also cross-reacts with mild PAS negative colorectal goblet cells when sections have been pre-treated with potassium hydroxide (to remove O-acetyl groups from sialic acid). These findings make it likely that the usual non-reactivity evidenced by TKH2 for normal colorectal goblet cells is due to the presence of sialic acid that is heavily O-acetylated. The reactivity of TKH2 for colorectal cancer mucin can be readily explained by the loss of sialic acid O-acetyl substituents and not necessarily by incomplete synthesis of mucin-type carbohydrate chains.
Jass
J R
JR
Department of Pathology, School of Medicine, University of Auckland, New Zealand.
Allison
L M
LM
Edgar
S
S
D000911:Antibodies, Monoclonal / Q000276:immunology*; D000912:Antibodies, Neoplasm / Q000276:immunology; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000276:immunology*; D002240:Carbohydrate Sequence; D015179:Colorectal Neoplasms / Q000276:immunology*; D003429:Cross Reactions / Q000276:immunology; D006801:Humans; D007124:Immunoenzyme Techniques; D007413:Intestinal Mucosa / Q000276:immunology*; D008969:Molecular Sequence Data; D009077:Mucins / Q000276:immunology*; D010503:Periodic Acid-Schiff Reaction
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D015295:Antigens, Tumor-Associated, Carbohydrate; D009077:Mucins; C055491:sialosyl-Tn antigen