P53 ALTERATION IN GASTRIC PRECANCEROUS LESIONS

It has been postulated that chronic atrophic gastritis, intestinal met aplasia, and dysplasia are precancerous stages of stomach tumorigenesi s. We investigated the timing of p53 alterations in these events of ga stric tumorigenesis. Each of 12 cases of archived tissue containing pr ecancerous and cancerous lesions were selected for the detection of p5 3 alterations. Accumulation of p53 protein was detected by immunohisto chemistry. Exons 5 to 8 of p53 gene were examined for mutations by pol ymerase chain reaction-single strand conformation polymorphism and DNA sequencing. p53 immunoreactivity was detected in 60% of the dysplasia cases and in 60% of the cases with carcinomas. p53 gene alterations w ere found in 37.5% of the metaplasia cases, 58.3% of the dysplasia cas es, and 66.7% of the cases with carcinomas. In 71% of the cases, mutat ions were shown as G:C --> A:T transition We conclude that mutation of the p53 gene is an early event in stomach tumorigenesis.