BACKGROUND: Alterations in the expression of p53 tumor suppressor protein is a frequent event in human cancer but the practical implications of this phenomenon are yet to be fully exploited. The objective of this study was to determine the value of p53 accumulation as a marker of tumor progression and prognosis of gastric carcinoma patients and to evaluate whether this parameter can be properly assessed prior to surgery. METHODS: The expression of p53 was studied immunohistochemically in 200 gastric carcinomas using paraffin embedded surgical specimens and endoscopic biopsies. The correlation between p53 expression in tumor tissue, selected clinicopathologic variables, and the course of the patients' disease were analyzed. RESULTS: Results showed that 42.5% of the gastric carcinomas expressed elevated levels of p53 protein. P53 accumulation positivity correlated with increasing tumor stage and size (P < 0.001 and P = 0.025, respectively). P53 positive tumors had a higher propensity for lymph node and distant metastases (P < 0.001). P53 accumulation was also more frequently detected in carcinoma from proximal rather than distal stomach (P = 0.027). In patients receiving potentially curative resection for advanced cancer, p53 accumulation was an independent parameter and the strongest for poor prognosis (RR = 3.7, P < 0.001). There was complete concordance between immunohistochemical detection of p53 in endoscopic and surgical material. CONCLUSIONS: A preoperative assessment of p53 expression in gastric carcinoma can be helpful to identify patients at high risk of metastatic spread to regional lymph nodes and independently to identify those with especially poor prognosis. When combined with routine procedures, this simple and inexpensive test might allow appropriate planning of better treatment strategies