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

Abstract

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.

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

“…However, in our hands, the villin and CDX2 expression are tightly coupled. Similar result was reported in BE too (Shi et al, 2008). A recent study found that knockdown of CDX2 in SW480 cells caused a clear down regulation of villin.…”

“…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).…”

“…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.…”

“…Immunohistochemical analyses of gastric intestinal metaplasia and cancer revealed that villin and Cdx2 expression are tightly coupled. Both of them are demonstrated to be useful maker for the diagnosis of Barrett's esophagus and intestinal metastasis in stomach (Dudouet et al, 1987;Fitzgerald et al, 1997;Athman et al, 2002;Niwa et al, 2005;Shi et al, 2008;Yamamichi et al, 2009).…”

Foveolar type dysplasia in Barrett esophagus

“…[10][11][12][13][14][15][16][17] Nevertheless, it has been reported that the Barrett esophagus columnar mucosa is 'intestinalized' when examined by immunohistochemical markers of intestinal differentiation, even in the absence of histological evidence of intestinal metaplasia, that is, goblet cells. [18][19][20][21][22][23] Thus supporting the current American College of Gastroenterology guidelines, which require the presence of intestinal metaplasia for the diagnosis of Barrett esophagus. 24 Clinical experience has suggested the presence of two cyto-architectural patterns of Barrett esophagus dysplasia and the terms type 1 and type 2 or adenomatous and non adenomatous (also known as 'foveolar/hyperplastic') akin to gastric dysplasia, have been applied to these patterns.…”