Sunday, February 21, 2016

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.

No comments: