title: TP53 deleted cells in de novo glioblastomas using fluorescence in situ hybridization.
abstract: Glioblastoma (GBM) has been known to have two distinct genetic pathways of tumorigenesis. Secondary GBM shows frequent TP53 mutation, but de novo (primary) GBM is usually independent of TP53 alteration. However, the subpopulation of TP53 altered cells in the latter tumor is obscure. In order to assess TP53 deleted cells in de novo GBM quantitatively, we performed dual color fluorescence in situ hybridization (FISH) for TP53 and centromere 17 in nine cases of de novo GBM with frozen surgical materials. Single TP53 signal cells indicating TP53 deletion were recognized in 8.7-35.6% (mean, 21.3%) among the nine cases. In addition, immunohistochemistry was performed for the Ki-67 antigen (MIB-1) and p53 protein in all nine cases. Labeling indices (LI) of MIB-1 ranged from 2.8 to 46.9% (mean, 20.8%). Between the group with the more dense subpopulation of TP53 deleted cells (15% or more) by FISH and the group with less subpopulation than the former, these LI of MIB-1 demonstrated statistically significant difference (respective means, 28.2% and 6.1%; P < 0.05). Conversely, LI of p53 protein shown to be 0-50.9% (mean, 24.9%) had no correlation with the subpopulation of TP53 deleted cells by FISH. Four cases who had higher LI of p53 protein (mean, 39.7%) than the subpopulation of TP53 deleted cells (mean, 12.7%), respectively, indicated the presence of many p53 protein immunoreactive cells without TP53 deletion. These results suggest that: (i) de novo GBM also has subpopulation of TP53 deleted cells; (ii) TP53 alteration, which may not be a major event, participates in cell proliferation of de novo GBM; and (iii) de novo GBM tends to have accumulation of wild-type p53 protein.
authors.affiliation: Department of Pathology, University of Tokushima School of Medicine, 3-18-15 Kuramoto, Tokushima 770-8503, Japan. hide@basic.med.tokushima-u.ac.jp
authors.forename: H
authors.initials: H
authors.lastname: Horiguchi
authors.forename: T
authors.initials: T
authors.lastname: Sano
authors.forename: T
authors.initials: T
authors.lastname: Hirose
mesh_terms: D000328:Adult; D000368:Aged; D002452:Cell Count; D002467:Cell Nucleus / Q000737:chemistry / Q000235:genetics; D002503:Centromere / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D016158:Genes, p53 / Q000235:genetics*; D005909:Glioblastoma / Q000737:chemistry / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D019394:Ki-67 Antigen / Q000032:analysis; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D015173:Supratentorial Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000235:genetics*
chemical_list: D019394:Ki-67 Antigen; D016159:Tumor Suppressor Protein p53