Comparative survival analysis of p53 gene mutations and protein accumulation in colorectal cancer

Immunohistochemical reactivity for p53 protein is common in various human malignancies. Increased intracellular concentration of p53, which is frequently, but not systematically, related to p53 mutation, has been proposed to be associated with poor prognosis in some tumor types. In colorectal cancer, this significance is still a matter of debate. To directly investigate the relationship between prognosis and p53 alterations, we screened a series of 72 colorectal carcinomas for overexpression and mutation of the p53 gene. Mutations in exons 5-9 of the p53 gene were assayed by single-strand conformation polymorphism and direct DNA sequencing, whereas p53 protein accumulation was detected in 10-mu m frozen tissue by immunostaining using 2 different monoclonal antibodies (PAb 1801 and DO7). Thirty-six tumors (50%) showed p53 overexpression. Nineteen of the 36 tumors which contained high levels of p53 protein were found to have missense point mutations. Using a multivariate survival analysis, stage, differentiation, p53 immunoreactivity and p53 mutation emerged as risk factors, but only the stage was significant. In univariate analysis, stage, differentiation and p53 immunoreactivity were significant prognostic indicators, while p53 mutation was at the borderline of significance.