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Background: Barrett’s mucosa is a risk factor for esophageal adenocarcinoma and should be detected at an early stage. CDX2 and liver—intestine (LI)-cadherin are intestine-specific markers.Aberrant CDX2 expression has been demonstrated in Barrett’s metaplasia, esophagitis, and intestinal metaplasia of the stomach. Methods: The relationship between CDX2 and LI-cadherin expression was investigated in normal gastroesophageal (n = 24) and in Barrett’s (n = 20) mucosa, in low-grade (n = 15) and high-grade (n = 13) intraepithelial neoplasia (IEN) as well as in esophageal adenocarcinoma (n = 16), using immunohistochemistry. Results: Nuclear positivity for CDX2 coupled with membranous expression of LI-cadherin was observed in about 70% of the epithelial cells of Barrett’s mucosa. The intensity of staining and the percentage of positive cells increased within the sequential steps of low-grade to high-grade IEN, whereas the normal cylindric epithelium lacked the expression of both. In adenocarcinoma, the expression of LI-cadherin and CDX2 was significantly weaker or absent. Conclusions: CDX2 and LI-cadherin are sensitive markers of intestinal metaplasia with or without dysplasia in the upper gastrointestinal tract. Both can be helpful for the early histologic diagnosis of Barrett’s esophagus and its subsequent lesions; however, they do not significantly discern between different grades of dysplasia. [ABSTRACT FROM PUBLISHER]