Subtyping of gliomas of various WHO grades by the application of immunohistochemistry

Histopathology. 2014 Feb;64(3):365-79. doi: 10.1111/his.12252. Epub 2013 Nov 5.

Abstract

Aims: In 2010, four subtypes (classical, proneural, mesenchymal, and neural) of glioblastoma multiforme (GBM) were defined by molecular genetic analyses. The objective of this study was to assess whether gliomas, independently of the type and grade, could be subdivided into protein-based subtypes.

Methods and results: A tissue microarray (TMA) approach was applied to incorporate tissue samples of low-grade and high-grade gliomas into five TMAs. High expression levels of epidermal growth factor receptor (EGFR), CD44, c-MER proto-oncogene tyrosine kinase (MERTK), platelet-derived growth factor receptor α, p53, oligodendrocyte transcription factor 2 (OLIG2) and isocitrate dehydrogenase 1 with the R132H mutation were assessed using immunohistochemistry (IHC). Glioma could be subdivided into four subtypes by IHC. The majority of the low-grade gliomas were of the proneural subtype, i.e. high p53 expression (63% of grade II). The classical subtype, with high EGFR and low p53 expression, was most common in GBMs (39%), followed by the proneural (29%) and mesenchymal (with high CD44 and MERTK expression) (29%) subtypes, a frequency that is in line with previously published data based on molecular genetics.

Conclusions: Assessment of the expression of the five proteins EGFR, CD44, MERTK, p53 and OLIG2 is sufficient for subtyping gliomas, and can be recommended for implementation in clinical practice for both low-grade and high-grade gliomas.

Keywords: glioma; immunohistochemistry; protein expression; subtyping.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Algorithms
  • Astrocytoma / classification
  • Astrocytoma / metabolism
  • Astrocytoma / pathology
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Biomarkers, Tumor / metabolism
  • Brain Neoplasms / classification
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / pathology*
  • ErbB Receptors / metabolism
  • Female
  • Glioblastoma / classification
  • Glioblastoma / metabolism
  • Glioblastoma / pathology
  • Glioma / classification
  • Glioma / metabolism*
  • Glioma / pathology*
  • Humans
  • Hyaluronan Receptors / metabolism
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Neoplasm Grading / methods
  • Nerve Tissue Proteins / metabolism
  • Oligodendrocyte Transcription Factor 2
  • Oligodendroglioma / classification
  • Oligodendroglioma / metabolism
  • Oligodendroglioma / pathology
  • Proto-Oncogene Proteins / metabolism
  • Receptor Protein-Tyrosine Kinases / metabolism
  • Receptor, Platelet-Derived Growth Factor alpha / metabolism
  • Retrospective Studies
  • Tissue Array Analysis
  • Tumor Suppressor Protein p53 / metabolism
  • World Health Organization
  • Young Adult
  • c-Mer Tyrosine Kinase

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Biomarkers, Tumor
  • CD44 protein, human
  • Hyaluronan Receptors
  • Nerve Tissue Proteins
  • OLIG2 protein, human
  • Oligodendrocyte Transcription Factor 2
  • Proto-Oncogene Proteins
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • EGFR protein, human
  • ErbB Receptors
  • MERTK protein, human
  • Receptor Protein-Tyrosine Kinases
  • Receptor, Platelet-Derived Growth Factor alpha
  • c-Mer Tyrosine Kinase