Diagnostics of pediatric supratentorial RELA ependymomas: integration of information from histopathology, genetics, DNA methylation and imaging

AbstractEpendymoma withRELA fusion has been defined as a novel entity of the revised World Health Organization 2016 classification of tumors of the central nervous system (CNS), characterized by fusion transcripts of theRELA gene and consequent pathological activation of the NFkB pathway. These tumors represent the majority of supratentorial ependymomas in children. The validation of diagnostic tools to identify this clinically relevant ependymoma entity is essential. Here, we have used interphase fluorescentin situ hybridization (FISH) forC11orf95andRELA, immunohistochemistry (IHC) for p65 ‐RelA and the recently developed DNA methylation‐based classification besides conventional histopathology, and compared the precision of the methods in 40 supratentorial pediatric brain tumors diagnosed as ependymomas in the past years. Reverse transcription PCR (RT‐PCR) and RNA sequencing wer e performed to explore discordant cases. Furthermore, we integrated imaging and clinical features as additional layers of information. The concordance between nuclear RelA expression by IHC andRELA FISH was 100%. Concordance between IHC and DNA methylation profiling, and between FISH and DNA methylation profiling was also high (96.4% and 95.2%, respectively). Thirty ‐four out of 40 (85%) cases were confirmed by integrated diagnoses as ependymal tumors, including 22RELA‐fused ependymomas (71% of ependymal tumors), twoYAP1 ‐fused ependymomas (6%), six non ‐RELA/non ‐YAP1 ependymomas (18...

Source: Brain Pathology - November 28, 2018 Category: Neurology Authors: M élanie Pagès, Kristian W. Pajtler, Stéphanie Puget, David Castel, Nathalie Boddaert, Arnault Tauziède‐Espariat, Stéphanie Picot, Marie‐Anne Debily, Marcel Kool, David Capper, Christian Sainte‐Rose, Fabrice Chrétien, Stefan M. Pfi Tags: Research Article Source Type: research