Since some gastric cancers are considered to originate from the intestinal metaplasia, it is likely that the adenomatous polyposis coli (APC) gene, the mutation of which causes adenomatous polyps in the colon, is associated with carcinogenesis of gastric cancer.
Columnar cells of specialized Barrett's epithelium express SI and are, therefore, phenotypically similar to those in incomplete intestinal metaplasia of the stomach with respect to intestinal gene expression.
Using a monoclonal antibody (PAb1801), nuclear p53 was detected in 22 of 45 (49%) cases of gastric carcinoma, and no staining for p53 was demonstrated in the adjacent normal epithelium, including areas of intestinal metaplasia.
Telomere reduction, tpr-met oncogenic rearrangement, overexpression of cripto, p53 mutations, adenomatous polyposis coli gene mutations and K-ras mutations, which are frequently associated with the well differentiated or intestinal type of stomach cancer, were found in intestinal metaplasia and adenoma of the stomach.
Immunohistochemistry detected 19 foci showing nuclear accumulation of p53 protein in non-neoplastic gastric mucosa in a total of 756 sections (477 of which contained intestinal metaplasia) from 16 resected stomachs containing gastric adenocarcinomas.
These results indicate that incomplete intestinal metaplasia is associated with increased cell turnover and p53 overexpression, possibly in response to various noxious or DNA-damaging stimuli.
Positive nuclear staining for the cyclin D1 protein in Barrett's disease with intestinal metaplasia was found in 38% of the male cases and 25% of the female cases, whereas in gastric metaplasia it was positive in 33% of men and 48% of women.
We generated DNA probes for CD44 variable region exons 11 (v6) to 14 (v9) and also for intronic sequences and examined the expression of aberrant CD44 transcripts in digestive tract carcinomas, colorectal adenomas and intestinal metaplasia of the stomach.
They may precede DNA replication error, DNA hypermethylation, CD44 abnormal transcript and p53 mutations, all of which occur in at least 30% of intestinal metaplasia as early events of multistep pathogenesis of well differentiated type gastric cancer.
Western blotting and RT-PCR demonstrated that CYP3A4 protein and mRNA were expressed in the liver and pyloric gland mucosa with intestinal metaplasia, but not in the fundic gland mucosa without intestinal metaplasia.
KAI1 was immunohistochemically detected in the lower part of fundic glands and intestinal metaplasia in non-cancerous gastric tissues, while only 11.0% (8/73) of cancerous tissues were shown to be positive.
These data indicate that MUC2 mucin is expressed in gastric regenerative epithelium in addition to intestinal metaplasia and intestinal type adenocarcinoma.