The prognostic value of overexpression of the p53-encoded protein was evaluated in 242 patients with gastric cancer. Formalin-fixed paraffin-embedded specimens of gastric adenocarcinomas were stained with the monoclonal antibody DO-7. 95 patients (39%) showed a high level of immunoreactivity (> or = 20% of cell nuclei staining positively), suggesting the presence of a mutation in the TP53 coding sequence. Overexpression of the p53 protein correlated significantly with stage of disease (P = 0.01), the presence of distant metastases (P = 0.04) and with the intestinal type of cancer (P = 0.04). No correlation between p53 overexpression and age, gender or the presence of the lymph node metastases was found. In univariate analysis, p53 immunoreactivity correlated significantly with survival (P = 0.0005). The median survival in the p53 high-level group was 19 months compared with 65 months in the p53 low-level group. In multivariate analyses, stage of disease and the presence of distant metastases emerged as independent prognostic factors, whereas p53 immunoreactivity did not (P = 0.08). The present results indicate that overexpression of the p53 protein is not an independent prognostic factor in patients with gastric cancer.