Immunohistochemical surrogate for BRAF V600E mutation

Quoted highlights  from: Tanboon J, Williams EA, and Louis DN. The Diagnostic Use of Immunohistochemical Surrogates for Signature Molecular Genetic Alterations in Gliomas. J Neuropathol Exp Neurol Vol. 75, No. 1, January 2016, pp. 4–18:

- The most common BRAF alteration is an activating mutation caused by a substitution of valine for glutamic acid at codon 600 (BRAF V600E) in exon 15.

- BRAF V600E status can be screened for using the mutation-specific BRAF V600E immunohistochemistry clone VE1... Only strong homogeneous unambiguous cytoplasmic staining should be interpreted as positive.

- While BRAFV600E can be found in a wide variety of brain tumors, BRAF fusions... are mostly limited to pilocytic astrocytomas (PAs).

- For tumor classification, aBRAF V600E mutation in a ganglion cell-rich lesion biopsied from infratentorial region favors ganglioglioma over PA.

- BRAF V600E mutations are present in pleomorphic xanthoastrocytoma (PXAs) with and without anaplasia (65%–70%), ganglioglioma (33%–60%), and [occasionally] PA, especially extracerebellar PA (6%–8%).

- In addition, BRAFV600E mutations are common in epithelioid glioblastomas (eGBM) (54%), which also tend to occur in children and relatively young adults.

- BRAF V600E mutations have also been reported in a small number of desmoplastic infantile astrocytomas, desmoplastic infantile gangliogliomas, and dysembryoplastic neuroepithelial tumors.

- A few diffuse astrocytomas in children and adults harbor BRAF V600E mutation; the tumors in adults show unusual histologic features such as partly circumscribed portions and spindle cells, and may associated with more favorable prognosis.

- Strong cytoplasmic staining patterns are often observed in PXA and eGBM; on the other hand, staining can be variable in glioneuronal tumors because BRAF can be diffusely positive in the tumor cell population or it can be limited to either a glial or neuronal component. For example, in ganglioglioma, mutant BRAF is predominantly expressed in neuronal tumor cells

- In glioneuronal tumors, BRAF V600E mutation is associated with activation of the mammalian target of rapamycin (mTOR) pathway, worse postoperative seizure outcome, and shorter recurrence-free survival.