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Diagnostics of pediatric supratentorial RELA ependymomas: integration of information from histopathology, genetics, DNA methylation and imaging
- Source :
- Brain Pathology (Zurich, Switzerland)
- Publication Year :
- 2018
- Publisher :
- Wiley, 2018.
-
Abstract
- Ependymoma with RELA 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 the RELA 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 fluorescent in situ hybridization (FISH) for C11orf95 and RELA, 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 were 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 and RELA 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 22 RELA‐fused ependymomas (71% of ependymal tumors), two YAP1‐fused ependymomas (6%), six non‐RELA/non‐YAP1 ependymomas (18%) and four ependymal/subependymal mixed tumors (12%). Ependymal/subependymal mixed tumors had an excellent clinical outcome despite the presence of histopathological signs of malignancy, suggesting that these tumors should not be diagnosed as classic ependymomas. DNA methylation profiling helped in the differential diagnosis of RELA‐fused ependymomas. IHC and FISH, which are available in the majority of pathology laboratories, are valuable tools to identify RELA‐fused ependymomas.
- Subjects :
- Male
0301 basic medicine
Ependymoma
Pathology
medicine.medical_specialty
YAP1
Malignancy
Pathology and Forensic Medicine
03 medical and health sciences
0302 clinical medicine
FISH
C11orf95‐RELA
medicine
Humans
Child
In Situ Hybridization, Fluorescence
Research Articles
Brain Neoplasms
business.industry
General Neuroscience
NF-kappa B
Transcription Factor RelA
Infant
Proteins
Supratentorial Neoplasms
Methylation
DNA Methylation
Subependymoma
medicine.disease
Immunohistochemistry
subependymoma
030104 developmental biology
HGNET
Child, Preschool
DNA methylation
Female
Histopathology
Neurology (clinical)
Differential diagnosis
business
Supratentorial Ependymoma
030217 neurology & neurosurgery
Research Article
Subjects
Details
- ISSN :
- 17503639 and 10156305
- Volume :
- 29
- Database :
- OpenAIRE
- Journal :
- Brain Pathology
- Accession number :
- edsair.doi.dedup.....ee9e587edaaf0c43242f614fdd501643