Journal Article

DKFZ-2017-05969

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Immunohistochemical analysis of H3K27me3 demonstrates global reduction in group-A childhood posterior fossa ependymoma and is a powerful predictor of outcome.

Panwalkar, P. ; Clark, J. ; Ramaswamy, V. ; Hawes, D. ; Yang, F. ; Dunham, C. ; Yip, S. ; Hukin, J. ; Sun, Y. ; Schipper, M. J. ; Chavez, L.DKFZ* ; Margol, A. ; Pekmezci, M. ; Chung, C. ; Banda, A. ; Bayliss, J. M. ; Curry, S. J. ; Santi, M. ; Rodriguez, F. J. ; Snuderl, M. ; Karajannis, M. A. ; Saratsis, A. M. ; Horbinski, C. M. ; Carret, A.-S. ; Wilson, B. ; Johnston, D. ; Lafay-Cousin, L. ; Zelcer, S. ; Eisenstat, D. ; Silva, M. ; Scheinemann, K. ; Jabado, N. ; McNeely, P. D. ; Kool, M.DKFZ* ; Pfister, S.DKFZ* ; Taylor, M. D. ; Hawkins, C. ; Korshunov, A.DKFZ* ; Judkins, A. R. ; Venneti, S.

2017
Springer Berlin

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Please use a persistent id in citations: doi:10.1007/s00401-017-1752-4

Abstract: Posterior fossa ependymomas (EPN_PF) in children comprise two morphologically identical, but biologically distinct tumor entities. Group-A (EPN_PFA) tumors have a poor prognosis and require intensive therapy. In contrast, group-B tumors (EPN_PFB) exhibit excellent prognosis and the current consensus opinion recommends future clinical trials to test the possibility of treatment de-escalation in these patients. Therefore, distinguishing these two tumor subtypes is critical. EPN_PFA and EPN_PFB can be distinguished based on DNA methylation signatures, but these assays are not routinely available. We have previously shown that a subset of poorly prognostic childhood EPN_PF exhibits global reduction in H3K27me3. Therefore, we set out to determine whether a simple immunohistochemical assay for H3K27me3 could be used to segregate EPN_PFA from EPN_PFB tumors. We assembled a cohort of 230 childhood ependymomas and H3K27me3 immunohistochemistry was assessed as positive or negative in a blinded manner. H3K27me3 staining results were compared with DNA methylation-based subgroup information available in 112 samples [EPN_PFA (n = 72) and EPN_PFB tumors (n = 40)]. H3K27me3 staining was globally reduced in EPN_PFA tumors and immunohistochemistry showed 99% sensitivity and 100% specificity in segregating EPN_PFA from EPN_PFB tumors. Moreover, H3K27me3 immunostaining was sufficient to delineate patients with worse prognosis in two independent, non-overlapping cohorts (n = 133 and n = 97). In conclusion, immunohistochemical evaluation of H3K27me3 global reduction is an economic, easily available and readily adaptable method for defining high-risk EPN_PFA from low-risk posterior fossa EPN_PFB tumors to inform prognosis and to enable the design of future clinical trials.

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Contributing Institute(s):

1. B062 Pädiatrische Neuroonkologie (B062)
2. KKE Neuropathologie (G380)
3. DKTK Heidelberg (L101)

Research Program(s):

1. 319H - Addenda (POF3-319H) (POF3-319H)

Appears in the scientific report 2017

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Database coverage:
; BIOSIS Previews ; Current Contents - Life Sciences ; Ebsco Academic Search ; IF >= 10 ; JCR ; NCBI Molecular Biology Database ; Nationallizenz ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Thomson Reuters Master Journal List ; Web of Science Core Collection

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