EZH2 expression in posterior fossa childhood ependymomas
Ependymoma is the third most common neuroepithelial tumour of the central nervous system (CNS) in childhood. There is an urgent need for better prognostic biomarkers and treatment options in childhood ependymoma.
EZH2 is a member of polycomb group (PcG) proteins which form polycomb repressive complexes (PRC) that modify chromatin, epigenetically repressing genesto regulate cellular differentiation and maintain stem cell self renewal.
EZH2 is aberrantly expressed in a number of cancers and is known to influence Wnt/β-catenin signalling.EZH2 expression can be modified by drugs such as Histone Deacetylase Inhibitors (HDACs) and Histone Methyltransferase Inhibitors.
We examined 30 cases of childhood posterior fossa ependymoma (18 WHO grade II Ependymomas, 12 Anaplastic Ependymoma WHO Grade III) from the CCLG tissue bank for EZH2 and beta catenin expression. This included 15 male and 15 female patients (age range 0.7-14.8 years). Standard immunohistochemistry on formalin- fixed tissue for EZH2 and beta catenin expression was undertaken on all cases, scored and compared with survival data.
In our small cohort of 30 patients EZH2 positive cases show a slightly better OS (p= 0.0581) with 78.3% survival in positive cases at 5 years compared to 50% in EZH2 negative cases, irrespective of WHO Grade. There was no relationship between beta catenin expression and OS in our cohort. There was no significant association of EZH2 expression with WHO Grade: 12/18 (66.7%) in ependymoma WHO Grade II were positive for EZH2 on immunohistochemistry compared with 10/12 (83.3%) anaplastic ependymomas WHO Grade III. Beta-catenin expression was found in 15/18 (83.3%) WHO Grade II ependymomas compared with 8/12 (66.7%) WHO Grade III ependymomas.
In our small cohort EZH2 positive cases showed a slightly better OS compared (p=0.0581) to EZH2 negative cases irrespective of WHO Grade. Further larger studies are required confirm the utility of EZH2 as a prognostic biomarker and drug target in childhood posterior fossa ependymomas
BRASH Brain Tumour Bank South West, North Bristol Trust; British Neuropathological Society.