EP-01HETEROGENEITY OF RELA PROTEIN EXPRESSION IN PAEDIATRIC EPENDYMOMA

INTRODUCTION: Ependymoma is the second commonest central nervous system malignancy in children. 50% of sufferers relapse and 80% of these subsequently die. Few prognostic factors have been identified but improved outcomes are seen in children over 3 years old and those with more complete surgical resection. Intratumour heterogeneity has not been previously described in ependymoma and refers to the diversity within a tumour. It has implications because, if present, single biopsies may ‘miss’ important areas whilst conventional treatments may ‘select’ for more resistant clonal populations. Overexpression of RelA protein has been described in ependymomas with the C11Orf95-RELA fusion gene; previously identified in 70% of supratentorial ependymomas. We aimed to interrogate a cohort of ependymomas for evidence of heterogeneity using RelA protein as a marker. METHODS: Tissue microarrays (TMAs) and whole sections from a group of children with ependymoma underwent immunohistochemistry for RelA protein. Each TMA core was scored as negative, positive or strongly positive (+/− nuclear staining) for RelA protein expression. RESULTS: 746 cores from 283 tumours (Mean = 2.63 cores/tumour) were scored. RelA protein was expressed in posterior fossa (34.2%), supratentorial (46.2%) and spinal (50.0%) tumours. 42 tumours had only 1 core available so were excluded. Of the remaining 241 tumours, 63 (26.1%) had multiple heterogeneous cores. Tumours with more cores were more likely to demonstrate heterogeneity. Heterogeneity was also seen across 23 tumour sections. CONCLUSIONS: Knowledge of ependymoma heterogeneity will facilitate approaches to diagnosis and development of targeted therapies. RelA protein is expressed heterogeneously in ependymoma and work based on protein expression in TMAs should therefore consider the risk of sampling bias. The extent of heterogeneity in ependymoma merits further study; including investigation of the relationship between RelA protein expression and the C11Orf95-RELA fusion genes and assessment of the association between RelA expression and clinical features.