Clinicopathological significance and survival influence of p53 protein expression in gastric carcinoma J Pinto-de-Sousa, F Silva, 1 L David, 1 D Leita ˜o, 1 M Seixas, 1 A Pimenta & M Cardoso-de-Oliveira Surgery B, Hospital S. Joa ˜o and Medical Faculty of the University of Porto, and 1 Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP) and Medical Faculty of the University of Porto, Porto, Portugal Date of submission 27 March 2003 Accepted for publication 21 August 2003 Pinto-de-Sousa J, Silva F, David L, Leita ˜o D, Seixas M, Pimenta A & Cardoso-de-Oliveira M (2004) Histopathology 44, 323–331 Clinicopathological significance and survival influence of p53 protein expression in gastric carcinoma Aims: Mutations in the gene coding for p53 protein are among the most frequent genetic alterations observed in human cancers. The relevance and biological significance of p53 expression in gastric carcinoma are far from being fully established. The aim of our study was to evaluate the influence of p53 detected by immunohistochemistry in the clinicopathological beha- viour of a series of gastric carcinoma cases. Methods and results: Samples from 163 patients treated by gastric resection for gastric carcinoma between 1988 and 1995 were used. Surgical specimens were evaluated for the presence of p53 protein detected by immunohistochemistry with a monoclonal antibody. Cases were classified as positive or negative for p53. Several clinicopathological parameters and c-erb B-2 expression were analysed in the same series and compared with the expression of p53. Cumulative survival was evaluated using univariate analysis and Cox model regression. p53 expression was identified in 41 carcinomas (25.2%) and was significantly associ- ated with venous invasion (P ¼ 0.049), lymph node metastases (P ¼ 0.01) and c-erb B-2 expression (P ¼ 0.003). All the parameters except gender, tumour size and Laure ´n’s classification influenced survival on univariate analysis. p53 expression cor- related with overall survival (P ¼ 0.006) and survival in the subgroup of patients with intestinal type carcinoma (P ¼ 0.04). In the subgroup of patients with carcinomas not expressing c-erb B-2, p53 expression significantly influenced cumulative survival (P ¼ 0.02). Conclusions: p53 expression is associated with the aggressive biological behaviour of gastric carcinomas and is related to cumulative survival. Keywords: p53, immunohistochemistry, gastric carcinoma, survival, prognosis Introduction The incidence of gastric carcinoma is decreasing worldwide, but still represents a major health problem in many developed and developing countries across the world. 1,2 Although surgery is the main tool for the treatment of gastric carcinoma, a complete resection can be achieved in only a small percentage of gastric carcinomas. 1,3–5 Therefore, new therapeutic options, such as primary or neoadjuvant chemotherapy, have recently been tried in several institutions, with the aim of improving the prognosis of gastric carcinoma patients. 4,6,7 The prognosis of gastric carcinoma is mainly dependent on the stage of the disease, but some biological markers, such as c-erb B-2, CD44, uAP and p53 have recently been regarded as new tools for the evaluation of the biological behaviour of gastric carcin- oma. 8–11 The p53 gene has been considered as the ‘guardian of the genome’ and is a tumour suppressor gene located on chromosome 17p, encoding a 53-kDa protein. 12 p53 plays a central role in cell-cycle regu- lation, in DNA repair and in cell apoptosis. Mutations in the p53 gene are observed in a large variety of Address for correspondence: J Pinto-de-Sousa MD, PhD, Servic ¸o de Cirurgia B, Hospital S. Joa ˜o, Alameda Prof Herna ˆni Monteiro, 4200 Porto, Portugal. e-mail: japs@med.up.pt Ó 2004 Blackwell Publishing Limited. Histopathology 2004, 44, 323–331