Down-regulation of a gastric transcription factor, Sox2, and ectopic expression of intestinal homeobox genes, Cdx1 and Cdx2: inverse correlation during progression from gastric/intestinal-mixed to complete intestinal metaplasia

Tsukamoto, Tetsuya; Inada, Ken‐ichi; Tanaka, Harunari; Mizoshita, Tsutomu; Mihara, Mami; Ushijima, Toshikazu; Yamamura, Yoshitaka; Nakamura, Shigeo; Tatematsu, Masae

doi:10.1007/s00432-003-0519-6

Cited by 122 publications

(186 citation statements)

References 62 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%

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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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“…Normally CDX2 is localized to the small and large bowel, 44,45 where it is responsible for the maintenance of intestinal phenotype, 21,22 including the upregulation of MUC2, an intestinal-type mucin, in goblet cells. 31,46 CDX2 expression has also been reported in 54% of gastric carcinomas, often in conjunction with MUC2 expression. 47 In this milieu, CDX2 is associated with tumor progression, during which tumors undergo an immunophenotypic shift from gastric phenotype (MUC5AC and/or MUC6 positive) to intestinal phenotype.…”

Section: Discussionmentioning

confidence: 99%

The dichotomy in carcinogenesis of the distal esophagus and esophagogastric junction: intestinal-type vs cardiac-type mucosa-associated adenocarcinoma

et al. 2011

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Adenocarcinoma of the distal esophagus and esophagogastric junction continues to rise in incidence. An intestinal metaplasia (Barrett esophagus)-dysplasia-carcinoma sequence induced by gastroesophageal reflux disease is well established. However, a significant number of adenocarcinomas in the vicinity of the esophagogastric junction are seen in the background of gastric/cardiac-type mucosa without intestinal metaplasia. Thus, the aim of this study was to investigate the role of Barrett esophagus (intestinal-type mucosa) in the classification and prognosis of tumors of the distal esophagus and esophagogastric junction. Clinicopathological and molecular characteristics were examined in 157 consecutively resected adenocarcinomas of the distal esophagus and esophagogastric junction and were compared between tumors arising in association with intestinal-type and cardiac-type mucosa. Intestinal-type mucosa-associated adenocarcinomas were more likely to be associated with younger age (P ¼ 0.0057), reflux symptoms (Po0.0001), proximal location (P ¼ 0.0009), lower T stage (Po0.0001), fewer nodal metastases (P ¼ 0.0001), absence of lymphatic (Po0.0001), venous (P ¼ 0.0060) or perineural (Po0.0001) invasion. Histologically, intestinal-type mucosa-associated tumors were more likely to be low-grade glandular tumors (P ¼ 0.0095) of intestinal or mixed immunophenotype (P ¼ 0.015) and express nuclear b-catenin (P ¼ 0.0080), whereas tumors arising in a background of cardiac-type mucosa were more frequently associated with EGFR amplification (P ¼ 0.0051). Five-year overall survival rate was significantly higher in patients with intestinal-type mucosa-associated tumors (28 vs 9%, P ¼ 0.0015), although no survival benefit was seen after adjusting for potential confounders. Our findings support the theory that multiple distinct pathways of tumorigenesis exist in the vicinity of the esophagogastric junction, including one in which tumors arise from dysplastic intestinal metaplasia (intestinal pathway), and one potentially involving dysplasia of the cardiac-type mucosa (non-intestinal pathway). Additional studies are warranted to further clarify their pathogenesis and the molecular mechanisms involved.

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“…In the process of intestinalization of stomach mucosa, changes in the expression of various genes, especially homeobox genes, have been reported. [44][45][46] Intestinal metaplasia can be caused in transgenic mice with targeted overexpression of Cdx2 in the stomach. 44 Alternatively, intestinal metaplasia may evolve from SPEM through a progressive change in cell mucin and trefoil expression similar to that observed in the ulcer-associated cell lineage by Wright et al 47 The results here suggest that a dynamic process of metaplasia may give rise first to SPEM in the setting of oxyntic atrophy followed by evolution of intestinal metaplasia under the influence of chronic inflammation.…”

Section: Spem Specifically Arises In and Spreads Out From The Intermementioning

confidence: 99%

Emergence of spasmolytic polypeptide-expressing metaplasia in Mongolian gerbils infected with Helicobacter pylori

Yoshizawa

Takenaka

Yamaguchi

et al. 2007

Laboratory Investigation

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Spasmolytic polypeptide (TFF2)-expressing metaplasia (SPEM) is observed in mucosa adjacent to human gastric cancer and in fundic glands showing oxyntic atrophy in Helicobacter felis-infected mice. Mongolian gerbils infected with Helicobacter pylori (Hp) develop goblet cell intestinal metaplasia and adenocarcinoma, but the presence of SPEM has not been studied in gerbils. We therefore have sought to examine the development of metaplastic mucosal changes in Hp-infected Mongolian gerbils. Mongolian gerbils were assigned to either uninfected controls or infected with Hp at 17 weeks of age. The animals were killed at 17, 20, 26, 31, 41 and 56 weeks of age. Stomach sections were stained using antibodies for TFF2, intrinsic factor, H/K-ATPase, BrdU and MUC2. Dual immunofluorescence staining for TFF2 with intrinsic factor and for TFF2 with MUC2 was performed. In uninfected animals, no SPEM or intestinal metaplasia was observed. Infected gerbils developed SPEM initially in the intermediate zone along the lesser curvature and subsequently spread out towards the greater curvature. In the earlier stages of infection, SPEM glands demonstrated TFF2 and intrinsic factor double staining cells. However, after 35 weeks of infection, the number of double staining SPEM cells decreased. While early in infection SPEM organized in straight glands, in the later stages of infections, SPEM glands became distorted or dilated along with the development of gastritis cystica profunda that was TFF2 positive. Goblet cell intestinal metaplasia developed only late in the infection. Dual staining for TFF2 and MUC2 showed glands containing both SPEM-and MUC2-positive goblet cell intestinal metaplasia. SPEM develops early in Hp infection in Mongolian gerbils, and alterations in gland morphology arise from SPEM glands during the course of gastric infection with goblet cell intestinal metaplasia developing subsequent to SPEM.

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Down-regulation of a gastric transcription factor, Sox2, and ectopic expression of intestinal homeobox genes, Cdx1 and Cdx2: inverse correlation during progression from gastric/intestinal-mixed to complete intestinal metaplasia

Abstract: Down-regulation of Sox2, besides ectopic expression of Cdx genes, may be important factors for the development of IM.

Cited by 122 publications

References 62 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

The dichotomy in carcinogenesis of the distal esophagus and esophagogastric junction: intestinal-type vs cardiac-type mucosa-associated adenocarcinoma

Emergence of spasmolytic polypeptide-expressing metaplasia in Mongolian gerbils infected with Helicobacter pylori

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