Article

p53 Mutations and Microsatellite Instabilities in the Subtype of Intestinal Metaplasia of the Stomach

Division of Gastroenterology, Department of Internal Medicine, College of Medicine, Catholic University of Korea, Seoul, Korea.
Journal of Korean Medical Science (Impact Factor: 1.27). 09/2002; 17(4):490-6. DOI: 10.3346/jkms.2002.17.4.490
Source: PubMed

ABSTRACT

To investigate the potential implication of the subtype of intestinal metaplasia in the progression to the gastric carcinoma, we analyzed the mutations of the p53 gene and microsatellite instability (MSI) both in the complete type (type I) and in the sulphomucin-secreting incomplete type (type III) intestinal metaplasia located adjacent to the gastric carcinoma. p53 mutations were observed in 13.3% of type I, in 6.6% of type III intestinal metaplasia, and in 40% of gastric carcinoma. The difference between p53 mutations observed in type I and type III intestinal metaplasia was not statistically significant. No identical mutation of the p53 gene was found in the intestinal metaplasia and carcinoma specimens from the patients. There was no case of intestinal metaplasia showing MSI. In gastric carcinomas, MSI was observed in six cases (40%). The cases harboring BAT-26 instability did not have the mutation of the p53 gene. These data suggest that intestinal metaplasia adjacent to gastric carcinoma, irrespective of its subtype, do not have the genetic alterations as showing in their carcinoma tissues.

Full-text preview

Available from: PubMed Central
  • Source

    Full-text · Article · Jan 2003 · Revista medica de Chile
  • [Show abstract] [Hide abstract]
    ABSTRACT: Multifocal chronic gastritis, associated to intestinal metaplasia, is considered a preneoplastic lesion, closely associated to intestinal type gastric cancer. To study the frequency of microsatellite instability (MSI) and loss of heterozygosity (LOH) in areas of chronic gastritis and intestinal metaplasia in gastric biopsies of patients without cancer. Gastric biopsy samples from 34 patients without cancer (22 with multifocal atrophic gastritis and 12 with diffuse antral gastritis), were studied. Glands from areas of chronic gastritis and intestinal metaplasia and lymphocytes, were collected using laser microdissection of paraffin embedded samples. The analysis of 15 mono and dinucleotide microsatellites was used to assess LOH and MSI. LOH and MSI were found in some of the markers in 55% (12/22) and 59% (13/22) of cases with intestinal metaplasia, respectively. Only one of 12 areas with diffuse atrophic gastritis had MSI and a different area had LOH (p < 0.05 or less, when compared with areas of multifocal atrophic gastritis). Three areas of normal epithelium in patients with multifocal atrophic gastritis, also had alterations. Most of these alterations were concordant with adjacent areas with intestinal metaplasia. LOH and MSI was found in areas of intestinal metaplasia in more than half of the studied cases and in few areas of atrophic gastritis without intestinal metaplasia. These findings suggest that genotypic alterations may precede phenotypic modifications and that intestinal metaplasia is a preneoplastic lesion.
    No preview · Article · Jan 2004 · Revista medica de Chile
  • [Show abstract] [Hide abstract]
    ABSTRACT: Chronic inflammation may be associated with microsatellite instability (MSI). To test the hypothesis that MSI frequently occurs in gastric intestinal metaplasia, we examined gastric biopsies from 58 subjects from an area of high risk for gastric cancer. These were selected to have 2 types of intestinal metaplasia: complete (31 subjects) and incomplete or mixed-type (27 subjects). None of the subjects had gastric cancer, but 95% had chronic inflammation with Helicobacter pylori. We used laser capture microdissection to retrieve metaplastic glands to compare with lymphocytes microdissected from the adjacent gastric mucosae in the same subjects. We performed microsatellite analysis using 6 microsatellite loci, including BAT26. None of the cases were found to have reproducible MSI, and only 1 case showed loss of heterozygosity at 1 marker, D3S1067. To test the sensitivity of our assay, we mixed templates to produce bands of different mobility and found that we could detect an aberrant microsatellite pattern if only 2% of the DNA showed that pattern. Our results indicate that MSI is a rare event in intestinal metaplasia in subjects who do not have gastric cancer.
    No preview · Article · Feb 2004 · Human Pathlogy
Show more