Immunohistochemistry on IDH 1/2, ATRX, p53 and Ki-67 substitute molecular genetic testing and predict patient prognosis in grade III adult diffuse gliomas

Brain Tumor Pathol. 2016 Apr;33(2):107-16. doi: 10.1007/s10014-016-0260-x. Epub 2016 Mar 11.

Abstract

The molecular subgrouping of diffuse gliomas was recently found to stratify patients into prognostically distinct groups better than histological classification. Among several molecular parameters, the key molecules for the subtype diagnosis of diffuse gliomas are IDH mutation, 1p/19q co-deletion, and ATRX mutation; 1p/19q co-deletion is undetectable by immunohistochemistry, but is mutually exclusive with ATRX and p53 mutation in IDH mutant gliomas. Therefore, we applied ATRX and p53 immunohistochemistry instead of 1p/19q co-deletion analysis. The prognostic value of immunohistochemical diagnosis for Grade III gliomas was subsequently investigated. Then, the same immunohistochmical diagnostic approach was expanded for the evaluation of Grade II and IV diffuse glioma prognosis. The results indicate immunohistochemical analysis including IDH1/2, ATRX, p53, and Ki-67 index is valuable for the classification of diffuse gliomas, which is useful for the evaluation of prognosis, especially Grade III gliomas and lower-grade gliomas (i.e., Grade II and III).

Keywords: ATRX; Glioma; IDH; Immunohistochemistry; Ki-67 index; p53.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / analysis*
  • Brain Neoplasms / diagnosis*
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / pathology
  • Brain Neoplasms / therapy
  • Combined Modality Therapy
  • DNA Helicases / analysis*
  • Female
  • Genetic Testing / methods*
  • Glioma / diagnosis*
  • Glioma / genetics*
  • Glioma / pathology
  • Glioma / therapy
  • Humans
  • Immunohistochemistry / methods*
  • Isocitrate Dehydrogenase / analysis*
  • Ki-67 Antigen / analysis*
  • Male
  • Middle Aged
  • Molecular Diagnostic Techniques*
  • Neoplasm Staging
  • Nuclear Proteins / analysis*
  • Predictive Value of Tests
  • Prognosis
  • Tumor Suppressor Protein p53 / analysis*
  • X-linked Nuclear Protein
  • Young Adult

Substances

  • Biomarkers, Tumor
  • Ki-67 Antigen
  • Nuclear Proteins
  • Tumor Suppressor Protein p53
  • IDH2 protein, human
  • Isocitrate Dehydrogenase
  • IDH1 protein, human
  • DNA Helicases
  • ATRX protein, human
  • X-linked Nuclear Protein