LG-19: IMMUNOHISTOCHEMISTRY IS HIGHLY SENSITIVE AND SPECIFIC FOR THE DETECTION OF BRAF V600E STATUS IN PEDIATRIC LOW-GRADE GLIOMA

INTRODUCTION: The BRAF-V600E mutation has been described in a broad spectrum of adult and pediatric cancers. Recently, tissue-specific discordances have been identified between immunohistochemistry (IHC) and sequencing methods for determining BRAFV600E status in colorectal carcinoma and melanoma, suggesting that the sensitivity and specificity of IHC needs to be determined for each cancer type. As BRAFV600E status in PLGG has been shown to have prognostic and therapeutic implications, there is a critical need to ensure accurate identification of patients whose PLGG harbour this mutation. We sought to investigate agreement between sequencing and IHC for BRAFV600E status specifically for PLGG. METHODS: Archival formalin-fixed, paraffin-embedded tissue was collected from 100 PLGG cases. BRAFV600E status was determined by both sequencing (digital-droplet PCR, ddPCR) and IHC (VE1 antibody). Discordant cases were re-evaluated by TaqMan PCR. RESULTS: Compared with ddPCR, the antibody had a sensitivity of 90% (34/38) and a specificity of 98% (52/53) for detecting the presence of the BRAFV600E mutation. For 8 cases there was insufficient tissue for sequencing but a result was obtained by IHC. There were 5 discordant cases. Additional molecular analysis confirmed the IHC result in 2 cases and the ddPCR result in 1 case. For 2 cases the re-evaluation is pending. CONCLUSIONS: The BRAFV600E IHC is a fast, accurate and cost-effective method for mutation detection in PLGG patients. Clinical use of the BRAFV600E antibody is a valuable alternative to conventional sequencing, allowing identification of patients with a potentially more aggressive clinical course and who may be eligible for targeted therapy.