Importance of underlying mesenchyme in the development of intestinal metaplasia and gastric cancer

The atrophy–intestinal metaplasia–gastric cancer sequence following H pylori infection is well recognised but the mechanisms are poorly understood. There has recently been great interest in the intestinal specific transcription factor Cdx2, which is expressed in human gastric mucosa with intestinal metaplasia. Over expression of Cdx2 in transgenic mice causes complete intestinal metaplasia of the gastric mucosa and subsequent development of gastric polyps and carcinoma. It is well known that the basement membrane derived from intestinal mesenchyme stimulates intestinal cell differentiation, but the role of mesenchyme in controlling intestinal metaplasia is uncertain. The present study examined the stomach of Cdx2 transgenic mice for the presence of the pericryptal fibroblasts (PCFs), which are normally only found in the intestine. Although there were no PCFs in the normal stomach, they were clearly detected when intestinal metaplasia had developed but disappeared as gastric …