Dysembryoplastic Neuroepithelial Tumors Share with Pleomorphic Xanthoastrocytomas and Gangliogliomas BRAF^V600E Mutation and Expression

Abstract

Pediatric cortical glioneuronal benign tumors mainly include gangliogliomas (GG) [differential diagnoses pilocytic astrocytomas (PA) and pleomorphic xanthoastrocytomas (PXA)] and dysembryoplastic neuroepithelial tumor (DNT). DNT include the specific form and the controversial non-specific form that lack the specific glioneuronal element. Our aims were to search for BRAF V600E mutation and CD34 expression in DNT, PXA, GG and PA to correlate BRAF V600E mutation with BRAF V600E expression and to evaluate their diagnostic and prognostic values. Ninety-six children were included. BRAF V600E mutation was studied by sequencing and immunohistochemistry; CD34 expression was analyzed by immunohistochemistry. BRAF V600E mutation was detected in PXA (60%), GG (38.7%), DNT (30%, including 3/11 specific and 3/9 non-specific forms) and PA (12.5%). BRAF V600E expression was recorded in PXA (60%), GG (45.2%) and DNT (30%). CD34 expression was recorded in PXA (60%), GG (58.1%), DNT (25%) and PA (12.5%). Neither CD34 expression nor BRAF V600E status was predictive of prognosis, except for PA tumors where CD34 expression was associated with a shorter overall survival. In conclusion, DNT shared with PXA and GG, BRAF V600E mutation and/or CD34 expression, which represent molecular markers for these tumors, and we recommend searching for CD34 expression and BRAF V600E mutation in all DNT, especially the nonspecific forms.

Epilepsy Related to Developmental Tumors and Malformations of Cortical Development

“…1d), desmoplastic infantile GGs [38], and DNTs [31,39]. The presence of the BRAF V600E mutation in DNTs strongly supports a relationship between DNTs and GGs, pointing to the pathogenic role of BRAF in different entities within the large spectrum of GNT, including other low-grade tumors arising in young age groups, such as pilocytic astrocytomas and pleomorphic xanthoastrocytoma [36,40].…”

BRAF‐V600E immunohistochemistry in a large series of glial and glial–neuronal tumors

“…We studied few cases of PXA (nine cases) and DNT (seven cases); this may explain why the frequencies of BRAF‐V600E mutation were lower than those reported in the literature (44.5% vs 66% for PXA/APXA and 0% vs 25% for DNT) (Chappé et al., 2013; Dougherty et al., 2010; Schindler et al., 2011). …”

“…As expected, the percentage of BRAF‐V600E mutant PA in our series was low (6.6%), which is comparable to the results obtained in other studies (Chappé et al., 2013; Schindler et al., 2011). It is interesting to note that the four mutant PA in our cohort were all of supratentorial location (basal ganglia, third ventricle, and optic pathways).…”

“…A BRAF‐V600E antibody has recently been commercialized (Capper et al., 2011; Colomba et al., 2013; Ritterhouse & Barletta, 2015), and it is sensitive and specific in detecting BRAF‐V600E mutation in cutaneous melanomas (Capper et al., 2011; Colomba et al., 2013; Long et al., 2013). In contrast, few studies have assessed the reliability of anti‐BRAF‐V600E immunohistochemistry (IHC) in CNS tumors (Behling et al., 2016; Chappé et al., 2013; Long et al., 2013) . Some groups have found that BRAF‐VE1 IHC was suboptimal in characterizing brain tumor tissue and that MB techniques are required for a reliable clinical assessment.…”

Dysembryoplastic neuroepithelial tumour: insight into the pathology and pathogenesis

“…BRAF is a RAF family member displaying the highest basal activity and being considered to play an important role in tumorigenesis [13,57] It is implicated in the so-called mitogen-activated protein kinase (MAPK) pathway [39].…”