ACCUMULATION OF WILD-TYPE P53 PROTEIN IN HUMAN ASTROCYTOMAS

We have previously described 10 astrocytomas with accumulation of p53 protein but no mutations in p53 exons 5-8, and we have suggested that they might represent overexpression of wild type protein or mutations in less conserved regions of the gene. To investigate these possibilit ies further, we studied the tumors with immunohistochemistry for wild type and mutant p53 protein and showed that all cases stained with the wild type PAb 1801 antibody but only one case stained with the mutant -specific PAb 240 antibody. To support the hypothesis that the accumul ated p53 protein is wild type in most cases, we used single-strand con formation polymorphism analysis and DNA sequencing to evaluate p53 exo ns 4, 9, and 10 and did not detect mutations at these loci. Although t he product of the MDM2 oncogene binds wild type p53 and may account fo r p53 accumulation, slot-blot analysis of these astrocytOmas did not d etect MDM2 gene amplification. Thus, evidence suggests that some astro cytomas may accumulate wild type p53 protein but not as a result of MD M2 gene amplification. Furthermore, PAb 1801 immunohistochemistry may not be an adequate method of screening astrocytomas for p53 mutations.