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Expression of small intestinal and colonic phenotypes in complete intestinal metaplasia of the human stomach

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Abstract

The incomplete intestinal metaplasia (IM) that is reported to be a risk factor for gastric carcinogenesis in man usually features sulfomucin production and thus is considered of colonic type. To cast light on the underlying mechanisms, we here examined the proportions of colonic and small intestinal phenotypes in IM by immunohistochemistry and real-time reverse transcription–polymerase chain reaction at the single isolated gland level. Carbonic anhydrase 1 (CA1) is a specific marker of colonic epithelial cells, whereas sucrase is specific to absorptive cells of the small intestine. Totals of 139 (23.5%) and 452 (76.5%) IM glands were judged to be CA1 positive and CA1 negative, respectively, in resected pyloric mucosa from cancer patients. The average score for MUC5AC in CA1-positive IMs was significantly lower than in CA1-negative counterpart tissue (P<0.0001), whereas the opposite was the case for sucrase (P<0.0001). High iron diamine–Alcian blue staining revealed CA1 expression to coincide with type I complete IM. The expression of CA1 mRNA strongly correlated with that of sucrase–isomaltase, and inversely with that of MUC5AC in isolated IM glands. In conclusion, CA1 could be colocalized with small intestinal proteins such as sucrase, but only rarely with the gastric mucin, MUC5AC. Its expression warrants further study, with the focus on stimulation and/or suppression mechanisms by gastric and intestinal transcription factors.

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Acknowledgements

This study was supported in part by a Grant-in-Aid for the Third-term Comprehensive 10-year Strategy for Cancer Control and a Grant-in-Aid for Cancer Research from the Ministry of Health, Labour and Welfare, Japan, and a Grant-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan. The authors thank Dr. Malcolm A. Moore for revision of the scientific English language and Ms. Hisayo Ban for expert technical assistance. The anti-sucrase antibody was a generous gift from Dr. Kazuyuki Hirano, Department of Pharmaceutics, Gifu Pharmaceutical University, Gifu, Japan.

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Correspondence to Tetsuya Tsukamoto.

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Tanaka, H., Tsukamoto, T., Mizoshita, T. et al. Expression of small intestinal and colonic phenotypes in complete intestinal metaplasia of the human stomach. Virchows Arch 447, 806–815 (2005). https://doi.org/10.1007/s00428-005-0040-1

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Keywords

  • Intestinal metaplasia
  • Carbonic anhydrase 1
  • Sucrase
  • Stomach
  • Gland isolation