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

Background: In the current model for the development of gastric cancer, regions of multifocal atrophic gastritis give rise to intestinal metaplasia, dysplasia and finally, adenocarcinoma., Aim: To study the frequency and characteristics of TP53 gene mutations in preneoplastic and neoplastic lesions of the stomach., Material and Methods: DNA sequencing of the TP53 gene was performed in 46 patients with gastric carcinoma. Normal mucosa, intestinal metaplasia and invasive adenocarcinoma tissues were obtained by scraping 6-micron histological sections from formalin-fixed and paraffin-embedded tissue., Results: DNA sequencing of exons 5-9 of the TP53 gene demonstrated a mutation in 31% of patients. These findings were seen both in tumoral tissue (13 cases) and in intestinal metaplasia (2 cases). Most mutations were found in exons 5 and 8, and the majority of them were transitions (10 out of 19 mutations)., Discussion: Patients with gastric cancer showed a frequency of TP53 mutations similar to that previously communicated in populations with low gastric cancer risk. Moreover, there was a predominance of transitions, genetic alterations that are identified with carcinogenesis associated with N-nitrosamine compounds. Finally, mutations of TP53 gene were detected in areas of intestinal metaplasia.