title: Association of TP53 mutation, p53 overexpression, and p53 codon 72 polymorphism with susceptibility to apoptosis in adult patients with diffuse astrocytomas.
abstract: Clarification of TP53 alterations is important to understand the mechanisms underlying the development of diffuse astrocytomas. It has been suggested that the alleles of TP53 at codon 72 differ in their ability to induce apoptosis in human cancers. The aim of this study was to analyze the possible association of TP53 mutation, p53 overexpression, and p53 codon 72 polymorphism with susceptibility to apoptosis in adult Brazilian patients with diffuse astrocytomas. We analyzed 56 surgical specimens of diffuse astrocytomas for alterations of TP53, using polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) direct sequencing. p53 and cleaved caspase 3 protein expression were assessed by immunohistochemistry. We found TP53 mutations in 19.6% (11 out of 56) of tumors tested, with the lowest mutation rate found in the cases of glioblastomas (8.8%) (p = 0.03). Only 16.1% of tumors tested showed cleaved caspase 3-positive staining, demonstrating that apoptosis is very inhibited in these tumors. All tumors having TP53 mutation and p53 accumulation had no expression of cleaved caspase 3. Additionally, no association was observed in tumors having proline and arginine alleles and expression of cleaved caspase 3. We concluded that clarification of the TP53 alterations allows a better understanding of the mechanisms involved in the progression of diffuse astrocytomas, and the allele status at codon 72 was not associated with apoptosis in these tumors.
authors.affiliation: Department of Neurology, School of Medicine, University of São Paulo, São Paulo, Brazil. unomiyuki@lim15.fm.usp.br
authors.forename: M
authors.initials: M
authors.lastname: Uno
authors.forename: S M
authors.initials: SM
authors.lastname: Oba-Shinjo
authors.forename: A
authors.initials: A
authors.lastname: Wakamatsu
authors.forename: N
authors.initials: N
authors.lastname: Huang
authors.forename: V Avancini
authors.initials: VA
authors.lastname: Ferreira Alves
authors.forename: S
authors.initials: S
authors.lastname: Rosemberg
authors.forename: Pires
authors.initials: P
authors.lastname: de Aguiar
authors.forename: C
authors.initials: C
authors.lastname: Leite
authors.forename: F
authors.initials: F
authors.lastname: Miura
authors.forename: R Junior
authors.initials: RJ
authors.lastname: Marino
authors.forename: M
authors.initials: M
authors.lastname: Scaff
authors.forename: S K
authors.initials: SK
authors.lastname: Nagahashi-Marie
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000235:genetics*; D001254:Astrocytoma / Q000235:genetics* / Q000473:pathology; D014408:Biomarkers, Tumor / Q000032:analysis; D053148:Caspase 3; D020169:Caspases / Q000032:analysis; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011110:Polymorphism, Genetic; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D016159:Tumor Suppressor Protein p53; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases