ACCUMULATION OF WILD-TYPE P53 IN ASTROCYTOMAS IS ASSOCIATED WITH INCREASED P21 EXPRESSION

Approximately one quarter of human astrocytomas show immunohistochemic al positivity for p53 protein but lack p53 gene mutations, which could reflect either an accumulation of wild-type p53 protein or an inadequ ate sensitivity of mutation detection. Since wild-type p53 up-regulate s p21 expression, increased p21 expression in those astrocytomas with p53 accumulation in the absence of mutations would argue that the prot ein was wild type in these tumors. We therefore compared p21 expressio n with p53 gene and protein status in 48 primary human astrocytomas. S ingle-strand conformation polymorphism analysis and direct sequencing of the p53 gene showed mutations in 11 tumors (22.9%), while immunohis tochemistry revealed positive staining in 19 cases (39.6%). Those tumo rs with p53 immunopositivity in the absence of p53 mutation had signif icantly increased p21 expression when compared to either mutant p53 or p53-immunonegative cases. Neither p53 nor p21 status correlated with proliferation indices, as assessed by Ki-67 immunohistochemistry. Thes e results support the hypotheses that functionally wild-type p53 accum ulates in some astrocytomas, and that alternative cell cycle checkpoin ts (such as the p16 pathway) may be more important than p21 in regulat ing proliferation in astrocytomas.