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.