Open AccessRevisiting TP 53 Mutations and Immunohistochemistry—A Comparative Study in 157 Diffuse Gliomas
Author(s) -
Takami Hirokazu,
Yoshida Akihiko,
Fukushima Shintaro,
Arita Hideyuki,
Matsushita Yuko,
Nakamura Taishi,
Ohno Makoto,
Miyakita Yasuji,
Shibui Soichiro,
Narita Yoshitaka,
Ichimura Koichi
Publication year - 2015
Publication title -
brain pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.986
H-Index - 132
eISSN - 1750-3639
pISSN - 1015-6305
DOI - 10.1111/bpa.12173
Subject(s) - immunohistochemistry , missense mutation , exon , frameshift mutation , immunostaining , microbiology and biotechnology , mutation , biology , pathology , cancer research , genetics , medicine , gene
The association between p 53 immunohistochemistry and TP 53 mutation status has been controversial. The present study aims to re‐evaluate the efficacy of p 53 immunohistochemistry to predict the mutational status of TP 53 . A total of 157 diffuse gliomas ( W orld H ealth O rganization grades II – IV ) were assessed by exon‐by‐exon DNA sequencing from exon 4 through 10 of TP 53 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 TP 53 mutation.