COMPARATIVE SURVIVAL ANALYSIS OF P53 GENE-MUTATIONS AND PROTEIN ACCUMULATION IN COLORECTAL-CANCER

Immunohistochemical reactivity for p53 protein is common in various hu man malignancies. Increased intracellular concentration of p53, which is frequently, but not systematically, related to p53 mutation, has be en proposed to be associated with poor prognosis in some tumor types. In colorectal cancer, this significance is still a matter of debate. T o directly investigate the relationship between prognosis and p53 alte rations, we screened a series of 72 colorectal carcinomas for overexpr ession and mutation of the p53 gene. Mutations in exons 5-9 of the p53 gene were assayed by single-strand conformation polymorphism and dire ct DNA sequencing, whereas p53 protein accumulation was detected in 10 -mu m frozen tissue by immunostaining using 2 different monoclonal ant ibodies (PAb 1801 and DO7). Thirty-six tumors (50%) showed p53 overexp ression. Nineteen of the 36 tumors which contained high levels of p53 protein were found to have missense point mutations. Using a multivari ate survival analysis, stage, differentiation, p53 immunoreactivity an d p53 mutation emerged as risk factors, but only the stage was signifi cant. In univariate analysis, stage, differentiation and p53 immunorea ctivity were significant prognostic indicators, while p53 mutation was at the borderline of significance.