Duodenal-content reflux into the esophagus leads to expression of Cdx2 and Muc2 in areas of squamous epithelium in rats.

The molecular events responsible for the transdifferentiation of epithelial cells of the esophagus to a columnar cell type are not well understood. Cdx2 has been detected in Barrett's esophagus, so we sought evidence of Cdx2 expression during the process of transdifferentiation of the esophageal squamous epithelium into a glandular phenotype. Thirty-two rats underwent an esophago-jejunostomy to produce esophagitis of 20, 25, 30, or 35 weeks of duration. The spectrum of esophageal lesions induced by chronic reflux was examined for expression of Cdx2 and Muc2 by immunohistochemistry. Five animals developed glandular metaplasia and adenosquamous carcinoma, two developed only glandular metaplasia, and two had adenosquamous carcinoma alone. Nuclear Cdx2 expression was detected in 57% (four of seven) and 43% (three of seven) of foci of glandular metaplasia and adenosquamous carcinomas, respectively. Cdx2 staining was detectable in some squamous and some mucus secreting cells. Perinuclear and perivacuolar staining of Muc2 was detected focally in 71% (five of seven) and 57% (four of seven) of areas with glandular metaplasia and adenosquamous carcinoma, respectively. We show that duodenal-content reflux into the esophagus switches on the expression of Cdx2 protein in esophageal keratinocytic cells, promoting a mucinous transdifferentiation process with secretion of intestinal mucin Muc2.

Expression of intestine-specific transcription factors, CDX1 and CDX2, in intestinal metaplasia and gastric carcinomas.

Intestinal metaplasia (IM) is part of a stepwise sequence of alterations of the gastric mucosa, leading ultimately to gastric cancer, and is strongly associated with chronic Helicobacter pylori infection. The molecular mechanisms underlying the onset of IM remain elusive. The aim of this study was to assess the putative involvement of two intestine-specific transcription factors, CDX1 and CDX2, in the pathogenesis of gastric IM and gastric carcinoma. Eighteen foci of IM and 46 cases of gastric carcinoma were evaluated by immunohistochemistry for CDX1 and CDX2 expression. CDX1 was expressed in all foci of IM and in 41% of gastric carcinomas; CDX2 was expressed in 17/18 foci of IM and in 54% of gastric carcinomas. In gastric carcinomas, a strong association was observed between the expression of CDX1 and CDX2, as well as between the intestinal mucin MUC2 and CDX1 and CDX2. No association was observed between the expression of CDX1 and CDX2 and the histological type of gastric carcinoma. In conclusion, these results show that aberrant expression of CDX1 and CDX2 is consistently observed in IM and in a subset of gastric carcinomas. The association of CDX1 and CDX2 with expression of the intestinal mucin MUC2, both in IM and in gastric carcinoma, indirectly implies that CDX1 and CDX2 may be involved in intestinal differentiation along the gastric carcinogenesis pathway.