[Microsatellite instability and loss of heterozygosity in neoplastic and preneoplastic gastric lesions].
BACKGROUND
Gastric cancer is the leading cause of cancer deaths in the general population in Chile, with mortality rates as high as 33.7 per 105 in males in the IX region. A chain of genetic and morphological events precedes the intestinal type of gastric carcinoma. One of them is the called multifocal atrophic gastritis often associated with intestinal metaplasia.


OBJECTIVE
To study the frequency of microsatellite instability (MSI) and loss of  heterocigozity (LOH) in neoplastic and preneoplastic lesions of gastric carcinoma, especially intestinal metaplasia.


METHODS
Ninety four gastric cancer biopsies were studied using laser capture microdissection, to obtain well defined cell populations from paraffin-embedded tissues: lymphocytes (control DNA), intestinal metaplasia and gastric cancer areas. Primer flanking microsatellite 15 highly polymorphic regions were used to study MSI and LOH. Radioactive PCR products were electrophoresed and exposed for autoradiography.


RESULTS
LOH was observed in 83% of gastric carcinomas and in 54% areas containing intestinal metaplasia. The most commonly altered regions were the CA repeat associated with the p53 gene and the 3p21 region. High grade MSI was observed in 11.7% of gastric cancer preparations and 17% of intestinal metaplasia associated to cancer with MSI-H phenotype.


CONCLUSIONS
MSI and LOH were frequently observed in intestinal metaplasia glands in patients with gastric carcinoma. The frequency of MSI-H phenotype in gastric patients was slightly lower than the one described in sporadic colorectal cancer not associated to HNPCC. The high incidence of genetic lesions in intestinal metaplasia area, support the idea that intestinal metaplasia is a genetically highly unstable cell population.
Roa
Juan Carlos
JC
Departamento de Patología, Universidad de La Frontera, Temuco, Chile. jcroa@ufro.cl
Araya
Juan Carlos
JC
Villaseca
Miguel Angel
MA
Roa
Iván
I
Correa
Pelayo
P
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D005260:Female; D005753:Gastric Mucosa / Q000473:pathology; D052138:Genes, Neoplasm; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D008679:Metaplasia / Q000235:genetics; D018895:Microsatellite Repeats / Q000235:genetics*; D008875:Middle Aged; D011230:Precancerous Conditions / Q000235:genetics* / Q000473:pathology; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology