title: Revisiting TP53 Mutations and Immunohistochemistry--A Comparative Study in 157 Diffuse Gliomas.
abstract: The association between p53 immunohistochemistry and TP53 mutation status has been controversial. The present study aims to re-evaluate the efficacy of p53 immunohistochemistry to predict the mutational status of TP53. A total of 157 diffuse gliomas (World Health Organization grades II-IV) were assessed by exon-by-exon DNA sequencing from exon 4 through 10 of TP53 using frozen tissue samples. Immunohistochemistry with a p53 antibody (DO-7) on paired formalin-fixed paraffin-embedded materials was assessed for the extent and intensity of reactivity in all cases. A total of 72 mutations were detected in 66 samples. They included 60 missense mutations, five nonsense mutations, four deletions and three alterations in the splicing sites. A receiver operating characteristic curve analysis revealed that strong p53 immunoreactivity in more than 10% of cells provided the most accurate prediction of mutation. Using this cutoff value, 52 of 55 immunopositive cases harbored a mutation, whereas only 14 of 102 immunonegative cases showed mutations, sensitivity and specificity being 78.8% and 96.7%. Tumors with frameshift mutations frequently showed negative immunostaining. Staining interpretation by an independent observer yielded comparable accuracy. We thus propose p53 immunohistochemistry as a moderately sensitive and highly specific marker to predict TP53 mutation.
authors.affiliation: Division of Brain Tumor Translational Research, National Cancer Center Research Institute, Tokyo, Japan; Department of Neurosurgery, University of Tokyo, Tokyo, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Takami
authors.forename: Akihiko
authors.initials: A
authors.lastname: Yoshida
authors.forename: Shintaro
authors.initials: S
authors.lastname: Fukushima
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Arita
authors.forename: Yuko
authors.initials: Y
authors.lastname: Matsushita
authors.forename: Taishi
authors.initials: T
authors.lastname: Nakamura
authors.forename: Makoto
authors.initials: M
authors.lastname: Ohno
authors.forename: Yasuji
authors.initials: Y
authors.lastname: Miyakita
authors.forename: Soichiro
authors.initials: S
authors.lastname: Shibui
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Narita
authors.forename: Koichi
authors.initials: K
authors.lastname: Ichimura
mesh_terms: D001921:Brain / Q000378:metabolism*; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005260:Female; D005910:Glioma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009154:Mutation / Q000235:genetics*; D012372:ROC Curve; D013223:Statistics as Topic; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism*
chemical_list: D016159:Tumor Suppressor Protein p53
keywords: Sanger sequence; astrocytoma; glioblastoma; immunohistochemistry; p53