Epithelioid GBMs show a high percentage of BRAF V600E mutation

Am J Surg Pathol. 2013 May;37(5):685-98. doi: 10.1097/PAS.0b013e31827f9c5e.


BRAF V600E mutation has been identified in up to 2/3 of pleomorphic xanthoastrocytomas (PXAs), World Health Organization grade II, as well as in varying percentages of PXAs with anaplastic features (PXA-A), gangliogliomas, extracerebellar pilocytic astrocytomas, and, rarely, giant cell glioblastoma multiforme (GC-GBMs). GC-GBMs and epithelioid GBMs (E-GBMs) can be histologically challenging to distinguish from PXA-A. We undertook this study specifically to address whether these 2 tumor types also showed the mutation. We tested our originally reported cohort of 8 E-GBMs and 2 rhabdoid GBMs (R-GBM) as well as 5 new E-GBMs (1 pediatric, 4 adult) and 9 GC-GBMs (2 pediatric, 7 adult) (n=24) for BRAF V600E mutational status. Twenty-one of 24 had sufficient material for IDH-1 immunostaining, which is usually absent in PXAs, PXA-As, and primary GBMs but present in secondary GBMs. Patients ranged in age from 4 to 67 years. BRAF V600E mutation was identified in 7/13 of E-GBMs, including 3 of our original cases; patients with mutation were aged 10 to 50 years. None of the 9 GC-GBMs or 2 R-GBMs manifested this mutation, including pediatric patients. The sole secondary E-GBM was the single case manifesting positive IDH-1 immunoreactivity. A high percentage of E-GBMs manifest BRAF V600E mutation, paralleling PXAs. All R-GBMs and GC-GBMs were negative, although larger multi-institutional cohorts will have to be tested to extend this result. BRAF V600E mutational analyses should be performed on E-GBMs, particularly in all pediatric and young-aged adults, given the potential for BRAF inhibitor therapy in this subset of GBM patients.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / pathology*
  • Child
  • Child, Preschool
  • DNA Mutational Analysis
  • Female
  • Glioblastoma / genetics*
  • Glioblastoma / pathology*
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Male
  • Microdissection
  • Middle Aged
  • Mutation
  • Proto-Oncogene Proteins B-raf / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Young Adult


  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf