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Gastric cancer remains the second most common cause of cancer deaths worldwide. 1 Human gastric carcinomas have been histologically classified into two main types: intestinal and diffuse. 2 Intestinal-type gastric carcinoma is frequently accompanied by widespread intestinal metaplasia that is mainly induced by Helicobacter pylori infection. Correa presented a hypothesis with respect to the mechanism of gastric carcinogenesis due to H pylori . 3- 5 H pylori infection is involved in the process of progression from normal gastric mucosa to superficial gastritis, chronic gastritis, atrophic gastritis, and finally to intestinal metaplasia. Intestinal-type gastric carcinoma is believed to arise via dysplasia from intestinal metaplasia.
Cdx1 and Cdx2, caudal related homeodomain transcription factors, are selectively localised in the mucosal epithelial nuclei of the small intestine and colon of the fetus and adult in both humans and mice. 6, 7 While normal gastric mucosa does not express transcription factors Cdx1 or Cdx2, strong nuclear immunoreactivity for Cdx1 was detected in human gastric intestinal metaplastic mucosa. 8 Furthermore, we and others have reported expression of Cdx1 and Cdx2 in human intestinal metaplastic mucosa. 9- 13 These findings suggest that Cdx1 and Cdx2 may play a pivotal role in the development of intestinal metaplasia in the human stomach.
Aberrant expression of Cdx2 in the stomach leading to the development of intestinal metaplasia in the transgenic mouse model was reported previously by us and others. 14, 15 In the normal intestine, Cdx2 is expressed at high levels in differentiated epithelial cells in the villi while Cdx1 is predominantly localised in undifferentiated cells of the proliferative crypt compartment. 6, 16- 18 Absorptive enterocytes, and goblet and enteroendocrine cells are located in villi that express Cdx2, but not Cdx1, while Paneth cells are located in crypts that express Cdx1. Silberg et al reported that Cdx2 induced intestinal metaplasia generated goblet cells and expressed intestine specific genes, but not enteroendocrine cells and Paneth cells. 15 In our Cdx2 expressing transgenic mouse stomach, intestinal metaplasia contained enterocytes, and goblet and enteroendocrine cells, but no Paneth cells, 14 indicating that Cdx2 induces differentiation of selected lineages of intestinal epithelial cells. It is unclear whether expression of Cdx1 in gastric mucosa might transdifferentiate the gastric lineage and, if so, comparing the nature of the Cdx1 induced...