The<i>Cdx-1</i>and<i>Cdx-2</i>homeobox genes in the intestine

Freund, Jean‐Noël; Domon‐Dell, Claire; Kédinger, Michèle; Duluc, Isabelle

doi:10.1139/o99-001

Cited by 137 publications

(72 citation statements)

References 123 publications

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“…However, it has been demonstrated that Cdx2 expression constitutes a very early event during intestinal development, as its presence is necessary for embryonic intestinal proliferation and differentiation. 15,17,19 The most interesting finding of this study was the presence of Cdx2-positive columnar cells in a substantial minority (38%) of cases lacking histological or histochemical features of intestinal metaplasia. The same feature was observed in five of the 22 (23%) cases from the group with intestinal metaplasia that included tissue samples devoid of goblet cells.…”

Section: Cdx2 In the Columnar-lined Esophagus Gm Groisman Et Almentioning

confidence: 58%

“…Human Cdx2 is a member of the caudalrelated homeobox gene family that activates an intestinal-specific gene transcription, which regulates normal intestinal development and differentiation and plays an important role in triggering cells towards the phenotype of differentiated enterocytes as well as in the maintenance of the phenotype. [15][16][17][18][19] Cdx2 expression in normal adult tissues is restricted to intestinal and colonic epithelium and a subset of pancreatic acinar and ductal cells. 22,24,27 In neoplasms, it is expressed by small and large intestinal epithelial tumors, by esophageal, urinary bladder and ovarian mucinous adenocarcinomas, and by a subset of pancreatobiliary adenocarcinomas.…”

Section: Discussionmentioning

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.…”

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confidence: 99%

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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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Section: Cdx2 In the Columnar-lined Esophagus Gm Groisman Et Almentioning

confidence: 58%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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

2004

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“…Intranscription factor CDX2, a member of the caudal-related homeobox gene family, normally is mainly expressed in small intestinal and colonic epithelia, but not in gastric epithelium (Freund et al, 1998). CDX2 plays an important role in mammalian early intestinal development and the maintenance of intestinal epithelia.…”

Section: Introductionmentioning

confidence: 99%

Effects of the Hippo Signaling Pathway in Human Gastric Cancer

Zhou¹,

Li²,

Zhang³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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Background/Aim: The Hippo signaling pathway is a newly discovered and conserved signaling cascade, which regulates organ size control by governing cell proliferation and apoptosis. This study aimed to investigate its effects in human gastric cancer. Methods: Tumor tissues (n=60), adjacent non-tumor tissues (n=60) and normal tissues (n=60) were obtained from the same patients with primary gastric cancer (GC). In addition, 70 samples of chronic atrophic gastritis (CAG) tissues were obtained from patients with intestinal metaplasia (IM) by endoscopic biopsy. Hippo signaling molecules, including Mst1, Lats1, YAP1, TAZ, TEAD1, Oct4 and CDX2, were determined by quantitative polymerase chain reaction (qPCR). Protein expression of Mst1, Lats1, YAP1, TEAD1 and CDX2 was assessed by immunohistochemistry and Western blotting. Results: Mst1, Lats1 and Oct4 mRNA expression showed an increasing tendency from GC tissues to normal gastric tissues, while the mRNA expression of YAP1, TAZ and TEAD1 was up-regulated (all P<0.01). Mst1 and Lats1 protein expression presented a similar trend with their mRNA expression. In addition, YAP1 and TEAD1 protein expression in GC was significantly higher than in the other groups (all P<0.01). CDX2 mRNA and protein expression in the CAG group were higher than in the other groups (all P<0.01). In GC, mRNA expression of Mst1, Lats1, Oct4, YAP1, TAZ, TEAD1 and CDX2 had a close correlation with lymphatic metastasis and tumor TNM stage (all P<0.01). Furthermore, protein expression of Mst1, Lats1 ,YAP1, TAZ, TEAD1 and CDX2 had a close correlation between each other (P<0.05). Conclusion: The Hippo signaling pathway is involved in the development, progression and metastasis of human gastric cancer. Therefore, manipulation of Hippo signaling molecules may be a potential therapeutic strategy for gastric cancer.

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“…21 CDX2 stimulates intestinal proliferation and differentiation through the transcriptional activation of intestine-specific proteins, including MUC2. 22 Several previous reports have suggested a tumorsuppressive role for CDX2 in human colorectal and gastric carcinogenesis. 23 CDX2 expression is associated with not only intestinal mucin phenotypes, 14,24 but also an early tumor stage [24][25][26][27][28][29][30] and improved prognosis in patients with gastric cancer.…”

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confidence: 98%

Prognostic significance of CDX2 and mucin expression in small intestinal adenocarcinoma

et al. 2014

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The clinicopathological and prognostic significance of CDX2 and mucin expression have not been comprehensively evaluated in small intestinal adenocarcinoma. Immunohistochemical microarray analyses of CDX2, MUC1, MUC5AC, and MUC6 protein expressions in 189 surgically resected small intestinal adenocarcinoma cases were examined and compared with various clinicopathologic variables, including survival. CDX2, MUC1, MUC5AC, and MUC6 expressions were observed in 43.4% (82 patients), 37.6% (71), 31.7% (60), and 21.7% (41) of patients, respectively. Whereas CDX2 expression was found to be associated with lowgrade tumors (P ¼ 0.034), fewer nodal metastases (P ¼ 0.019), and less perineural invasion (P ¼ 0.049) in small intestinal adenocarcinoma patients, patients expressing MUC1 tended to demonstrate high-grade (P ¼ 0.021) and nodular or infiltrative (P ¼ 0.020) tumors. On the basis of the combined CDX2, MUC1, MUC5AC, and MUC6 expression patterns, small intestinal adenocarcinoma patients were further classified as intestinalAmong these immunophenotypes, intestinal-type patients demonstrated more frequent distal (jejunal or ileal; P ¼ 0.033), tubular (P ¼ 0.039), and low-grade tumors (P ¼ 0.004) and significantly better survival according to univariate (Po0.0001) and multivariate (P ¼ 0.001) analyses. In summary, intestinal immunophenotype adenocarcinomas are associated with distal (jejunal or ileal), tubular, and low-grade tumors and better survival outcomes. Hence, CDX2 and mucin immunohistochemical staining may provide better estimations of survival after surgical resection and intestinal immunophenotype could therefore be used as a better prognostic indicator of small intestinal adenocarcinoma. Modern Pathology (2014Pathology ( ) 27, 1364Pathology ( -1374 doi:10.1038/modpathol.2014 published online 7 March 2014 Keywords: adenocarcinoma; CDX2; immunohistochemistry; mucin; prognosis; small intestine Primary small intestinal adenocarcinomas account for only 5% of malignant neoplasms in the gastrointestinal tract despite the long length of the small intestine and the significant mucosal coverage over the entire gastrointestinal tract. 1 In 2013, it is estimated that 8810 Americans will be diagnosed with small intestinal adenocarcinoma. 1 Despite recent improvements in the detection of the small intestinal adenocarcinomas, including improved imaging techniques and endoscopic modalities, the diagnosis of small intestinal adenocarcinomas is usually made at an advanced clinical stage and the 5-year survival rate is only 41.2%. 2 Several clinicopathologic factors, including lymph node metastasis and the distal locations of these tumors (jejunum and ileum), are known as the most important independent prognostic factors. 2 Although several molecular alterations, including KRAS, TP53, and DPC4/SMAD4 mutations and the overexpression of cyclinD1, are known to be involved in small intestinal adenocarcinoma carcinogenesis, [3][4][5][6]

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TheCdx-1andCdx-2homeobox genes in the intestine

Cited by 137 publications

References 123 publications

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

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

Effects of the Hippo Signaling Pathway in Human Gastric Cancer

Prognostic significance of CDX2 and mucin expression in small intestinal adenocarcinoma

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