title: Subtyping of gliomas of various WHO grades by the application of immunohistochemistry.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Department of Pathology and Cytology, Uppsala University Hospital, Uppsala, Sweden.
authors.forename: Svetlana N
authors.initials: SN
authors.lastname: Popova
authors.forename: Michael
authors.initials: M
authors.lastname: Bergqvist
authors.forename: Anna
authors.initials: A
authors.lastname: Dimberg
authors.forename: Per-Henrik
authors.initials: PH
authors.lastname: Edqvist
authors.forename: Simon
authors.initials: S
authors.lastname: Ekman
authors.forename: Göran
authors.initials: G
authors.lastname: Hesselager
authors.forename: Fredrik
authors.initials: F
authors.lastname: Ponten
authors.forename: Anja
authors.initials: A
authors.lastname: Smits
authors.forename: Linda
authors.initials: L
authors.lastname: Sooman
authors.forename: Irina
authors.initials: I
authors.lastname: Alafuzoff
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D001254:Astrocytoma / Q000145:classification / Q000378:metabolism / Q000473:pathology; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism; D001932:Brain Neoplasms / Q000145:classification / Q000378:metabolism* / Q000473:pathology*; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D005909:Glioblastoma / Q000145:classification / Q000378:metabolism / Q000473:pathology; D005910:Glioma / Q000145:classification / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading / Q000379:methods; D009419:Nerve Tissue Proteins / Q000378:metabolism; D000076104:Oligodendrocyte Transcription Factor 2; D009837:Oligodendroglioma / Q000145:classification / Q000378:metabolism / Q000473:pathology; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000378:metabolism; D012189:Retrospective Studies; D046888:Tissue Array Analysis; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014944:World Health Organization; D055815:Young Adult; D000076202:c-Mer Tyrosine Kinase
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D014408:Biomarkers, Tumor; D066246:ErbB Receptors; D018960:Hyaluronan Receptors; D009419:Nerve Tissue Proteins; D000076104:Oligodendrocyte Transcription Factor 2; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D020794:Receptor Protein-Tyrosine Kinases; D020796:Receptor, Platelet-Derived Growth Factor alpha; D016159:Tumor Suppressor Protein p53; D000076202:c-Mer Tyrosine Kinase; C497483:CD44 protein, human; C000715470:MAS1 protein, human; C405708:OLIG2 protein, human; C495901:TP53 protein, human; C512478:EGFR protein, human; C097072:MERTK protein, human
keywords: glioma; immunohistochemistry; protein expression; subtyping