Nestin protein expression is an independent prognostic marker in ependymoma and discriminates WHO II ependymoma with poor outcome

We have previously shown that the ependymoma cancer stem cell model DKFZ-EP1NS recapitulate ependymoma tumorigenesis at the histological, molecular and clinical level in an orthotopic murine model. EP1NS cells are characterized by a high expression of the neuronal stem cell marker nestin and a stem cell expression signature. We have therefore examined nestin expression in a large cohort of 379 ependymoma primary tumors. High protein expression of nestin, as assessed by immunohistochemistry, is associated with poor prognosis. Most importantly, nestin separates grade II ependymomas into two groups with distinct survival, with nestin positive grade II ependymomas having the same poor prognosis as grade III anaplastic ependymomas. Additional information is gained when combining nestin IHC with classifications according to cytogenetic groups 1–3, and/or posterior fossa group A and B (PFA/PFB). Multivariable analysis demonstrates that nestin positivity is an independent marker for poor progression-free (PFS) and overall survival (OS). Finally, analysis of nestin co-regulated genes in two separate datasets (n=75 and n=102 ependymoma samples, respectively) reveals co-regulation of developmental and epigenetic processes. In summary, our data suggest nestin as a useful novel marker for ependymoma risk stratification, improving diagnostic precision in differentiating grade II and III, which is virtually arbitrary in daily practice.

*These authors contributed equally to this work