Monoclonal antibody TKH2 to the cancer-associated epitope sialosyl Tn shows cross-reactivity with variants of normal colorectal goblet cell mucin

Pathology. 1994 Oct;26(4):418-22. doi: 10.1080/00313029400169112.

Abstract

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.

MeSH terms

  • Antibodies, Monoclonal / immunology*
  • Antibodies, Neoplasm / immunology
  • Antigens, Tumor-Associated, Carbohydrate / immunology*
  • Carbohydrate Sequence
  • Colorectal Neoplasms / immunology*
  • Cross Reactions / immunology
  • Humans
  • Immunoenzyme Techniques
  • Intestinal Mucosa / immunology*
  • Molecular Sequence Data
  • Mucins / immunology*
  • Periodic Acid-Schiff Reaction

Substances

  • Antibodies, Monoclonal
  • Antibodies, Neoplasm
  • Antigens, Tumor-Associated, Carbohydrate
  • Mucins
  • sialosyl-Tn antigen