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.

Immunostaining of Increased Expression of Enhancer of Zeste Homolog 2 (EZH2) in Diffuse Midline Glioma H3K27M-Mutant Patients with Poor Survival

“…PRC2 is susceptible to either gain- or loss-of-function alterations in malignancy [23]. According to the PRC2 structural basis described in Justin et al [27] (the structural basis of the oncogenic H3K27M inhibition of PRC2), the binding of PRC2 and the nucleosome involves multiple interactions of PRC2 components.…”

“…Immunostaining was positive for IDH1R132H with strong cytoplasmic staining [21]. The ATRX and p53 staining positive cut-off value was 10% nuclear staining [22, 23]. Labeling index evaluation for Ki-67 was based on nuclear staining in tumor cells [24].…”

Multicentric Glioma Develops via a Mutant IDH1-Independent Pathway: Immunohistochemical Study of Multicentric Glioma

“…Anti-human PTEN (1: 100, Dako) was used as the primary antibody. The antibody for p53 was prepared using anti-human p53 protein (1: 100, Dako) [18] . The antibody against Ki-67/MIB-1 was an anti-human Ki-67 antigen clone MIB-1 (1: 25, Dako).…”

Analysis of the gene-protein interaction network in glioma

“…BCL2A1 is a potential biomarker that influences preoperative seizure occurrence and postoperative seizure control in patients with low-grade gliomas (You et al, 2013;Li et al, 2014). TP53 is a pivotal gene frequently mutated in diffuse gliomas and particularly in astrocytic tumors (Takami et al, 2014); CCL2 was among the first identified in gliomas, and it is overexpressed in colon carcinomas. Its silencing inhibits colon cancer cell proliferation or increases the sensitivity to apoptotic stimuli of glioma cells, suggesting an oncogenic role (Carrillode Sauvage et al, 2012).…”