Chronology of p53 protein accumulation in gastric carcinogenesis.

Abstract

P53 Protein accumulation in early gastric carcinoma was studied in relation to the histological type (Lauren classification) and the type of growth pattern, including the chronology of p53 protein accumulation during carcinogenesis. Forty five, paraffin embedded gastrectomy specimens from early carcinomas were examined for the presence of chronic atrophic gastritis, subtypes of intestinal metaplasia, and dysplasia. The Lauren type and the type of growth pattern were reassessed for all early carcinomas. p53 Protein accumulation was examined using the monoclonal antibody DO-7. Complete absence of p53 protein accumulation was observed in normal gastric mucosa, chronic atrophic gastritis, and intestinal metaplasia, irrespective of subtype. In gastric dysplasia (one mild, two moderate, and one severe), only severe dysplasia was p53 positive. Intestinal type (n = 20) and diffuse type early gastric carcinomas (n = 25) were p53 positive in 70% and 52% of cases, respectively. Both tumour types differed significantly in the percentage of p53 positive tumour cells per tumour (p < 0.01) and in staining intensity (p < 0.05). No significant difference in p53 protein accumulation was found between early carcinomas with different types of growth pattern. It is concluded that p53 protein accumulation--usually reflecting missense p53 gene mutation--seems to be a late event in gastric carcinogenesis. Moreover, it is suggested that missense p53 gene mutation occurs in a final pathway common to both intestinal and diffuse type of early gastric carcinoma. Finally, the types of growth pattern do not seem to differ in p53 protein accumulation.