HETEROGENEITY OF SUBCELLULAR-LOCALIZATION OF P53 PROTEIN IN HUMAN GLIOBLASTOMAS

Immunohistochemical analysis of the p53 protein in human glioblastomas with known genetic profiles of p53 mutations and allele losses on chr omosome 17p demonstrated a heterogeneous pattern of subcellular compar tmentalization of the p53 protein. Tumors with a single wild type copy of the p53 gene but with allelic deletions on chromosome 17p exhibit nuclear and/or cytoplasmic accumulation of p53, whereas tumors with bo th copies of the wild type gene and no allele losses on chromosome 17 do not accumulate p53. Glioblastomas with one normal and one mutated c opy of the p53 gene and allelic deletions on 17p distal to p53, on the other hand, show predominantly cytoplasmic staining, probably origina ting from the wild type p53 protein. Furthermore, tumors with mutation s in the same codon of p53 display quite different intracellular distr ibution suggesting that, in addition to the genotype of p53, the intra cellular microenvironment of a particular tumor is important in determ ining the subcellular localization of the p53 protein.