Kapoor, N.; Hulbert, M.; Haqquani, M.; Yu, L.G.; Bodger, K.
April 2003
Gut;Apr2003 Supplement 1, Vol. 52, pA42
Academic Journal
Background: Cdx2 is an intestinal transcription factor that is a key regulator of development and homeostasis of intestinal epithelium. In the adult, Cdx2 expression is confined to the small and large intestine. Neo-expression occurs in gastric intestinal metaplasia and ectopic gastric expression of Cdx2 leads to an intestinalised mucosa in transgenic mice. Preliminary reports suggest that Cdx2 is expressed in BM. We aimed to examine Cdx2 expression within various histological sub-types of BM and during malignant progression. Methods: With informed consent, 68 oesophageal surveillance biopsies from 52 patients with BM were studied. Formalin-fixed, paraffin-embedded sections were subject to immunohistochemistry using an anti-Cdx2 mAb (BioGenex) and an automated avidin-biotinbased system. Control sections comprised normal colon and duodenum. Both H&E and mucin staining (Gomori's aldehyde fushcin) were employed in serial sections to identify and type foci of metaplastic epithelium. Nuclear immunostaining was scored semi-quantitatively (0-absent; 1-focally absent or weak; 2-strongly positive). We also screened confluent TE7 cells (oesophageal adenocarcinoma) for Cdx2 expression by immunoblotting of cell lysates (CACO-2 cells were employed as positive control). Results: All examples of squamous mucosa, cardiac/fundic-type glands and deep oesophageal glands were negative for Cdx2 expression. Staining intensity within intestinal-type mucosa and dysplasia is shown in the table. No Cdx2 expression was identified in immunoblots of TE7 adenocarcinoma cells. Conclusions: Neo-expression of Cdx2 is almost invariable in SIM but does not occur in gastric-type variants of Barrett's oesophagus. Down-regulation of Cdx2 may occur during oesophageal malignant progression, consistent with a tumour suppressor function. The molecular mechanisms regulating Cdx2 expression during oesophageal carcinogenesis require further study.


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