HIGH-FREQUENCY OF P53 PROTEIN ACCUMULATION WITHOUT P53 GENE MUTATION IN HUMAN JUVENILE PILOCYTIC, LOW-GRADE AND ANAPLASTIC ASTROCYTOMAS

We analysed 31 non-glioblastoma astrocytomas for alterations in p53 pr otein expression and for mutations in the p53 gene. Immunohistochemist ry detected p53 protein accumulation in 71% (five of seven) of juvenil e pilocytic astrocytomas (WHO grade I), 63% (five of eight) of astrocy tomas (WHO grade II), and 63% (10 of 16) of anaplastic astrocytomas (W HO grade III). The single strand conformation polymorphism (SSCP) assa y of exons 2-11 of the p53 gene and direct DNA sequencing identified p 53 mutations in 14% (one of seven) of grade I, 25% (two of eight) of g rade II, and 19% (three of 16) of grade III astrocytomas. This is the first report of a p53 mutation in grade I juvenile pilocytic astrocyto mas. Immunohistochemistry and SSCP analyses gave concordant results in 55% (17 of the 31) of the tumors. A total of 14 tumors, 60-80% within each grade, showed p53 protein accumulation in the absence of detecta ble mutations of the p53 gene. No mdm-2 gene amplification was found i n these tumors. The similar frequency of p53 alterations in tumors of grades I-III suggests that the p53 gene plays a significant role early in the formation of astrocytomas rather than late in tumor progressio n to higher grade. The data suggest that mechanisms other than p53 gen e inactivation by mutation or mdm-2 complex formation result in the ac cumulation of P53 protein in > 70% of non-glioblastoma astrocytomas.