Molecular outcome prediction in intracranial ependymoma based on WDR16 expression status

Ependymomas are glial tumors of the brain and the spinal cord. Despite histological similarities, recent data suggest that the entity ependymoma encompasses multiple molecularly and clinically different subgroups. An incontrovertible fact of ependymoma is the highly variable clinical behaviour, hindering outcome prediction and consequently risk-adapted therapy. By performing whole genome expression profiling of 65 intracranial ependymomas, we identified the kinocilia-marker gene WD repeat domain 16 (WDR16) as a novel biomarker, which allows outcome prediction in ependymoma of all locations of the CNS. Elevated WDR16 mRNA expression was significantly associated with non-relapsing tumors (p<0.001) and survival of the patients (p<0.001). These results were validated on protein level by performing immunohistochemistry on an ependymoma tissue microarray containing a non-overlapping cohort of 406 primary tumor samples. Kaplan-Maier analysis confirmed a very strong association of high WDR16 expression and favourable prognosis (PFS: p<0.001; OS: p<0.001). The accuracy and clinical applicability of a WDR16-based stratification system was confirmed by comparing our marker-based model to the recently published risk-stratification model for intracranial ependymoma which is based on chromosome aberrations (Korshunov et al. 2010). In conclusion, the addition of WDR16 to complement clinical and cytogenetic and information might be useful for clinical application because it is fast, cost-effective and also feasible in formalin-fixed, paraffin-embedded samples.