Genetic and immunohistochemical analyses of p53 independently predict regional metastasis of gastric cancers

Either p53 gene mutation or immunohistochemical detection of p53 protein ha s not been consistently shown to have prognostic significance in human canc ers, including gastric carcinomas. One hypothesis to explain this inconsist ency is that some p53 mutations and p53 protein accumulation are not indica tive of tumor progression. To test this hypothesis, we categorized p53 stat us in 105 gastric carcinomas according to types of mutations, numerical sco res of immunohistochemical staining (MC), or combinations thereof. The p53 status was then correlated with metastasis to liver or peritoneum, Gastric cancers with no p53 mutations were significantly less likely to metastasize than tumors with mutations, Intermediate MC scores were inversely associat ed with metastasis. A substantial number of gastric cancers (31 of 105) sho wed positive p53 immunostaining without detectable mutations (p53-/IHC+), w hich suggested an accumulation of wild-type p53 protein, and also a signifi cantly lon er risk for metastasis. After adjusting for depth of invasion an d lymph node involvement, the p53-/IHC+ combination predicted low metastati c risk better than either p53- or IHC+ with intermediate scores. These find ings suggest that an accumulation of wild-type p53 protein occurs in gastri c cancer cells and represents a stress-response mechanism that lowers metas tatic potential.