Aberrant expression of CDX2 in Barrett's epithelium and inflammatory esophageal mucosa

Eda, Akashi; Osawa, Hiroyuki; Satoh, Kiichi; Yanaka, Ichiro; Kihira, Ken; Ishino, Yumiko; Mutoh, Hiroyuki; Sugano, Kentaro

doi:10.1007/s005350300001

Cited by 178 publications

(195 citation statements)

References 34 publications

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“…Ectopic CDX2 expression was believed related with intestinal metaplasia of the stomach, and Barrett's esophagus(BE) in human beings (Eda et al, 2003;Guo et al, 2004;Shi et al, 2008;Tsukamoto et al, 2004). Silberg DG found that the expression of CDX2 in transgenic mice can lead occurrence of IM in gastric mucosa (Silberg et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

“…Ectopic CDX2 expression is considered to involve in the development of intestinal metaplasia and play significant roles in oncogenesis in gastrointestinal tract and its expression has been demonstrated in intestinal metaplasia of the stomach, and Barrett's metaplasia in human beings. So, CDX2 has concerned recently as an early marker for IM epithelium (Eda et al, 2003;Guo et al, 2004;Tsukamoto et al, 2004;Shi et al, 2008). Villin is a tissue-specific actin-binding cytoskeletal protein that is associated with actin filaments in the microvilli and terminal web of epithelial cells.…”

Section: Expression Of Cdx2 and Villin In Gastric Cardiac Intestinal mentioning

confidence: 99%

See 1 more Smart Citation

Expression of CDX2 and Villin in Gastric Cardiac Intestinal Metaplasia and the Relation with Gastric Cardiac Carcinogenesis

Xiao¹,

Ru²,

Sun³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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Section: Discussionmentioning

confidence: 99%

Section: Expression Of Cdx2 and Villin In Gastric Cardiac Intestinal mentioning

confidence: 99%

Expression of CDX2 and Villin in Gastric Cardiac Intestinal Metaplasia and the Relation with Gastric Cardiac Carcinogenesis

Xiao¹,

Ru²,

Sun³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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“…Further evidence for the potential role of acid on differentiation programs in the esophageal-gastrointestinal tract has recently been reported by Marchetti et al (2003), who showed that CDX2, a key factor for intestinal differentiation, is activated through acid exposure of esophageal keratinocytes. This pHtriggered transdifferentiation might play a pivotal role in the generation of Barrett's mucosa in gastroesophageal reflux disease (Eda et al, 2003).…”

Section: Dimmler Et Almentioning

confidence: 96%

Transcription of Sonic Hedgehog, a Potential Factor for Gastric Morphogenesis and Gastric Mucosa Maintenance, Is Up-regulated in Acidic Conditions

Dimmler

Brabletz

Hlubek

et al. 2003

Laboratory Investigation

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SUMMARY:Gastric body mucosa atrophy predisposes one to gastric cancer. Disturbances in the gastric differentiation process might play a role in the evolution of gastric atrophy. Sonic hedgehog (Shh) has recently been implicated as a crucial factor in gastric organogenesis and gland differentiation. In this study we investigated the expression of key factors in the Shh pathway, namely Shh and its receptor Patched (Ptc), in normal and pathologic stomach mucosa. Furthermore, the potential role of pH for Shh dysregulation was analyzed. Ten gastric biopsy specimens each from normal gastric mucosa, chronic nonatrophic gastritis, atrophic gastritis, and gastric cancer were included. Expression of Shh and Ptc was analyzed by immunohistochemistry. In normal body mucosa and in nonatrophic body gastritis, Shh was strongly expressed in parietal cells. Ptc was also expressed in gastric chief cells. Shh expression was almost completely lost in atrophic gastritis and in gastric cancer and absent in intestinal metaplasia. Ptc was markedly reduced in atrophy and only weakly positive in intestinal metaplasia and gastric cancer. In in vitro experiments, gastric cancer cell line 23132 was found positive for Shh. In long-term culture as well as in culture conditions with low pH, transcription of Shh in 23132 was significantly increased in quantitative reverse transcription PCR analyses. We concluded that the decreased expression of the Shh pathway in atrophic gastritis and gastric cancer might reflect altered differentiation processes within the gastric unit and contributes to the development of gastric atrophy. The increase of gastric pH might play a role in the development of gastric mucosa atrophy via reduction of Shh transcription. (Lab Invest 2003, 83:1829 -1837.

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“…22,24,27 In contrast, esophageal and gastric intestinal metaplastic cells are Cdx2 positive. 20,21,23,25,26 Further studies will help to confirm or refute Cdx2 as a sensitive and specific marker of intestinal differentiation.…”

mentioning

confidence: 99%

“…[15][16][17][18][19] The expression of Cdx2 in adult non-neoplastic tissues has been shown to be restricted to normal intestinal epithelium, normal pancreatic epithelial cells, and gastric and esophageal intestinal metaplasia. [20][21][22][23][24][25][26][27] In the gastrointestinal tract, Cdx2 is strongly and diffusely expressed in the nuclei of normal small and large intestinal epithelial cells, including absorptive, goblet, endocrine and Paneth cells; in the pancreatic epithelium its expression is focal and patchy. 22,24,27 Normal esophageal and gastric epithelial cells are Cdx2 negative.…”

mentioning

confidence: 99%

Expression of the intestinal marker Cdx2 in the columnar-lined esophagus with and without intestinal (Barrett's) metaplasia

2004

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Barrett's esophagus is diagnosed when goblet cells are found in the lower esophageal mucosa. However, the distribution of these cells is patchy and they may not represent the earliest marker of intestinal metaplasia. Cdx2 is a transcription factor whose expression in normal tissues is restricted to intestinal-type epithelium. Its distribution in the columnar-lined esophagus with and without intestinal metaplasia has been seldom studied. We evaluated Cdx2 expression in lower esophageal biopsies from 90 patients with endoscopic diagnosis of short segment Barrett's esophagus, including 45 consecutive cases showing intestinal metaplasia (goblet cells present in hematoxylin eosin and/or Alcian blue stains) and 45 consecutive cases without goblet cells. 25 samples of cardiac-type mucosa without intestinal metaplasia biopsied from the stomach served as controls. All cases with intestinal metaplasia revealed Cdx2 reactivity in goblet cells and adjacent nongoblet columnar cells. Dysplastic foci, seen in five cases from this group, were Cdx2 positive. In the group without goblet cells, Cdx2 was focally expressed by columnar cells in 17 (38%) cases. All control cases were Cdx2 negative. Strips of Alcian blue-positive nongoblet columnar cells ('columnar blues') were observed in 11 (24%) of the cases without intestinal metaplasia. All these foci were Cdx2 negative. In conclusion, Cdx2 is a highly sensitive marker for Barrett's esophagus. It is also expressed in a significant minority of cases of columnar-lined esophagus without goblet cells, suggesting that it may detect intestinal phenotypic modifications in the absence of goblet cells. Accordingly, Cdx2 immunostaining could help identify patients with Barrett's metaplasia in cases where no goblet cells are visible in biopsies from the columnar-lined esophagus. Finally, lack of Cdx2 expression in the 'columnar blues' suggests that these cells are not diagnostic of intestinal metaplasia.

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Aberrant expression of CDX2 in Barrett's epithelium and inflammatory esophageal mucosa

Abstract: We report here, for the first time, that CDX2 is expressed in patients with Barrett's epithelium and inflammatory esophageal mucosa. These findings imply that the expression of CDX2 may be an early event leading to the development of Barrett's esophagus.

Cited by 178 publications

References 34 publications

Expression of CDX2 and Villin in Gastric Cardiac Intestinal Metaplasia and the Relation with Gastric Cardiac Carcinogenesis

Expression of CDX2 and Villin in Gastric Cardiac Intestinal Metaplasia and the Relation with Gastric Cardiac Carcinogenesis

Transcription of Sonic Hedgehog, a Potential Factor for Gastric Morphogenesis and Gastric Mucosa Maintenance, Is Up-regulated in Acidic Conditions

Expression of the intestinal marker Cdx2 in the columnar-lined esophagus with and without intestinal (Barrett's) metaplasia

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