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Gastric Cancer

, Volume 9, Issue 3, pp 156–166 | Cite as

Gastric-and-intestinal mixed-type intestinal metaplasia: aberrant expression of transcription factors and stem cell intestinalization

  • Tetsuya Tsukamoto
  • Tsutomu Mizoshita
  • Masae Tatematsu
Review article

Abstract

Helicobacter pylori plays a causative role in the development of chronic atrophic gastritis, intestinal metaplasia (IM), and stomach cancer. Although IM has long attracted attention as a putative preneoplastic lesion for stomach cancers, its clinicopathologic significance has yet to be clarified in detail. Using gastric and intestinal epithelial cell markers, IM was here divided into two major types: a gastric-and-intestinal (GI) mixed type and a solely intestinal (I) type. In the former, gastric and intestinal phenotypic markers appeared not only at the glandular but also at the cellular level. Furthermore, neuroendocrine cells also showed intestinalization along with their exocrine counterparts. In animal models, GI-type IM was found to appear first, followed by the solely I type. Summarizing these data, it was suggested that IM might be caused by the gradual intestinalization of stem cells from the GI to the I type. The molecular mechanisms of IM include the ectopic expression of CDX1, CDX2, OCT-1, and members of the Erk pathway. Suppression of the expression of gastric transcription factors such as SOX2, genes that are involved in the Sonic hedgehog pathway, and RUNX3, a tumor suppressor gene, could be additional relevant alterations. The expression of PDX1 may also be associated with pseudopyloric gland metaplasia and IM. Detailed analysis of gene regulation may shed light on the molecular bases of gastric lesions, leading to strategies for chemoprevention.

Key words

Gastric-and-intestinal mixed-type intestinal metaplasia Stem cell Transcription factor 

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Copyright information

© International and Japanese Gastric Cancer Association 2006

Authors and Affiliations

  • Tetsuya Tsukamoto
    • 1
  • Tsutomu Mizoshita
    • 1
  • Masae Tatematsu
    • 1
  1. 1.Division of Oncological PathologyAichi Cancer Center Research InstituteNagoyaJapan

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