CDX2 and Villin Are Useful Markers of Intestinal Metaplasia in the Diagnosis of Barrett Esophagus

Division of Anatomical Pathology, Hunter Area Pathology Service, Newcastle, Australia.
American Journal of Clinical Pathology (Impact Factor: 2.51). 04/2008; 129(4):571-7. DOI: 10.1309/UWK3NAHV31GFHM3J
Source: PubMed


The identification of intestinal metaplasia (IM) in the esophagus is necessary for the selection of patients with Barrett esophagus (BE) for surveillance. We studied 108 esophageal biopsy and resection specimens, clinically diagnosed as BE, and stained them for CDX2, villin, HepPar-1, and cytokeratin (CK) 7 to investigate sensitivity for identifying IM. H&E-stained sections showed definite goblet cells in 94 cases. CDX2 and villin were positive in all 94 cases. Of 38 cardia- and 9 fundic-type mucosa samples associated with BE, 13 (34%) and 0 (0%) displayed CDX2 positivity and 21 (55%) and 1 (11%) displayed villin positivity, respectively. HepPar-1 was positive in 54 (57%) of 94 cases with IM and negative in the associated cardia- and fundic-type mucosa. A full-thickness CK7 staining pattern was present in 90 (96%) of samples with IM and 22 (58%) and 0 (0%) of the associated cardia- and fundic-type mucosa, respectively. None of 20 control samples of morphologically normal gastric mucosa stained for CDX2 or villin. CDX2 and villin are sensitive markers for early-stage IM and can supplement the histologic identification of this premalignant condition in the esophagus.

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    • "Dudouet et al., 1987; Fitzgerald et al., 1997; Athman et al., 2002; Niwa et al., 2005; Shi et al., 2008; Yamamichi et al., 2009). "
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    ABSTRACT: To determine whether CDX2 and villin protein expression are associated with intestinal metaplasia (IM) in gastric cardiac mucosa and to explore the relationship with evolution of gastric cardiac adenocarcinoma (GCA). We studied 143 gastric cardiac biopsy or resection specimens from Henan province China, including 25 cardiac gastritis specimens with IM, 65 dysplasia specimens with IM and 35 gastric cardiac adenocarcinoma specimens and stained them for CDX2 and villin by the immunohistochemical SP method. 15 normal gastric cardiac biopsy specimens were also collected as control. (1) Normal gastric mucosa presented no CDX2 and villin expression. The positive rates of CDX2 protein in cardiac gastritis with IM, dysplasia with IM, and carcinoma tissues were 84.0% (21/25), 66.7% (32/48) and 36.4% (20/55), respectively. While the positive rates of villin protein in cardiac gastritis with IM, dysplasia with IM, and carcinoma tissues were 76.0% (19/25), 70.8% (34/48) and 45.5% (25/55), respectively.There were significant differences among the three groups for both CDX2 and villin (P<0.01). Spearman's rank correlation coefficient(rho) showed a close correlation between the two proteins (r=0.843, P<0.01) and both were positively related with tumor differentiation (both P<0.05), but not associated with age, sex, invasion and metastasis of lymph node (P>0.05). Our results suggest that ectopic expression of CDX2 and villin may be involved in early-stage IM and tumorigenesis in gastric cardia and the expression of villin may be regulated by CDX2.
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    ABSTRACT: The application of immunohistochemistry in the diagnostic gastrointestinal pathology is similar to many other organ systems. The most commonly used markers are epithelial cell markers such as cytokeratin AE1/3, cytokeratin 7 and cytokeratin 20, and markers for common mesenchymal tumors such as CD117, CD34, S100, desmin, etc. Tumors of neuroendocrine origin are probably more commonly seen in the digestive and pulmonary systems. A synaptophysin and chromogranin immunostain generally can confirm their ­neuroendocrine nature. Use of immunohistochemical studies to evaluate dysplasia in Barrett’s esophagus is still investigational, although many have found p53 overexpression helpful in confirming dysplasia, particularly in high-grade dysplasia. The use of immunohistochemical studies in nonneoplastic diseases of the gastrointestinal tract is limited. Finally, immunohistochemistry, like GCDFP-15 immunostain, may play a critical role in differentiating certain metastases, such as lobular carcinoma of the breast, from primary tumors, including gastric signet ring cell carcinoma. KeywordsDysplasia-Carcinoma-GIST-Neuroendocrine-Metastasis-Keratin-CD117-Synaptophysin
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