Abstract
Ependymomas comprise 8 % of all intracranial tumors in children <15 years. Recent studies revealed that some supratentorial ependymomas express neuronal antigens and that high expression of neurofilament protein light polypeptide (NEFL) correlates with better clinical outcome. We retrospectively analyzed an expanded panel of proteins in 6 supratentorial, 15 posterior fossa and 4 spinal pediatric ependymomas by immunohistochemistry. Expression of high and low affinity neurotrophin receptors TrkA (NTRK1) and p75 (NGFR), pan-neuronal markers NeuN (RBFOX3) and synaptophysin, radial glial marker SOX9, adhesion molecules CD56 (NCAM) and CD44, junctional protein connexin 43 (GJA1), glial fibrillary acidic protein (GFAP), epithelial membrane antigen and proliferation associated antigen Ki-67 were evaluated in a semi-quantitative or quantitative (Ki-67 and NeuN-index) fashion. We found p75 and NeuN to be expressed at significantly higher levels in supratentorial versus infratentorial tumors and GFAP to be expressed at significantly higher levels in infratentorial lesions. In conclusion, immunohistochemical expression of p75, NeuN and GFAP differed in ependymomas depending on tumor topography supporting the view of divergent cells of origin. However, because of the small sample size the results are of preliminary nature and replication in a larger cohort would be desirable.
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Kaatsch P, Rickert CH, Kuhl J, Schuz J, Michaelis J (2001) Population-based epidemiologic data on brain tumors in German children. Cancer 92:3155–3164
Korshunov A, Neben K, Wrobel G, Tews B, Benner A, Hahn M et al (2003) Gene expression patterns in ependymomas correlate with tumor location, grade, and patient age. Am J Pathol 163:1721–1727
Taylor MD, Poppleton H, Fuller C, Su X, Liu Y, Jensen P et al (2005) Radial glia cells are candidate stem cells of ependymoma. Cancer Cell 8:323–335
Palm T, Figarella-Branger D, Chapon F, Lacroix C, Gray F, Scaravilli F et al (2009) Expression profiling of ependymomas unravels localization and tumor grade-specific tumorigenesis. Cancer 115:3955–3968
Dyer S, Prebble E, Davison V, Davies P, Ramani P, Ellison D et al (2002) Genomic imbalances in pediatric intracranial ependymomas define clinically relevant groups. Am J Pathol 161:2133–2141
Godfraind C, Kaczmarska JM, Kocak M, Dalton J, Wright KD, Sanford RA et al (2012) Distinct disease-risk groups in pediatric supratentorial and posterior fossa ependymomas. Acta Neuropathol 124:247–257
Ellison DW, Kocak M, Figarella-Branger D, Felice G, Catherine G, Pietsch T et al (2011) Histopathological grading of pediatric ependymoma: reproducibility and clinical relevance in European trial cohorts. J Negat Results Biomed 10:7
Carlén M, Meletis K, Göritz C, Darsalia V, Evergren E, Tanigaki K et al (2009) Forebrain ependymal cells are Notch-dependent and generate neuroblasts and astrocytes after stroke. Nat Neurosci 12:259–267
Rodriguez FJ, Scheithauer BW, Robbins PD, Burger PC, Hessler RB, Perry A et al (2007) Ependymomas with neuronal differentiation: a morphologic and immunohistochemical spectrum. Acta Neuropathol 113:313–324
Andreiuolo F, Puget S, Peyre M, Dantas-Barbosa C, Boddaert N, Philippe C et al (2010) Neuronal differentiation distinguishes supratentorial and infratentorial childhood ependymomas. Neuro Oncol 12:1126–1134
Johnson RA, Wright KD, Poppleton H, Mohankumar KM, Finkelstein D, Pounds SB et al (2010) Cross-species genomics matches driver mutations and cell compartments to model ependymoma. Nature 466:632–636
Louis DN, Ohgaki H, Wiestler OD, Cavenee WK (eds) (2007) WHO classification of tumours of the central nervous system. IARC, Lyon
Sharma MK, Mansur DB, Reifenberger G, Perry A, Leonard JR, Aldape KD et al (2007) Distinct genetic signatures among pilocytic astrocytomas relate to their brain region origin. Cancer Res 67:890–900
Rousseau E, Palm T, Scaravilli F, Ruchoux M-M, Figarella-Branger D, Salmon I et al (2007) Trisomy 19 ependymoma, a newly recognized genetico-histological association, including clear cell ependymoma. Mol Cancer 6:47
Phillips HS, Kharbanda S, Chen R, Forrest WF, Soriano RH, Wu TD et al (2006) Molecular subclasses of high-grade glioma predict prognosis, delineate a pattern of disease progression, and resemble stages in neurogenesis. Cancer Cell 9:157–173
Cheng W-Y, Kandel JJ, Yamashiro DJ, Canoll P, Anastassiou D (2012) A multi-cancer mesenchymal transition gene expression signature is associated with prolonged time to recurrence in glioblastoma. PLoS One 7:e34705
Nikoletopoulou V, Lickert H, Frade JM, Rencurel C, Giallonardo P, Zhang L et al (2010) Neurotrophin receptors TrkA and TrkC cause neuronal death whereas TrkB does not. Nature 467:59–63
Chiaretti A, Aloe L, Antonelli A, Ruggiero A, Piastra M, Riccardi R et al (2004) Neurotrophic factor expression in childhood low-grade astrocytomas and ependymomas. Childs Nerv Syst 20:412–419
Kordes U, Hagel C (2006) Expression of SOX9 and SOX10 in central neuroepithelial tumor. J Neurooncol 80:151–155
de Bont JM, Kros JM, Passier MMCJ, Reddingius RE, Sillevis Smitt PAE, Luider TM et al (2008) Differential expression and prognostic significance of SOX genes in pediatric medulloblastoma and ependymoma identified by microarray analysis. Neuro Oncol 10:648–660
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Hagel, C., Treszl, A., Fehlert, J. et al. Supra- and infratentorial pediatric ependymomas differ significantly in NeuN, p75 and GFAP expression. J Neurooncol 112, 191–197 (2013). https://doi.org/10.1007/s11060-013-1062-1
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DOI: https://doi.org/10.1007/s11060-013-1062-1