title: Chromosome 1q gain and tenascin-C expression are candidate markers to define different risk groups in pediatric posterior fossa ependymoma.
abstract: Intracranial classic (WHO grade II) and anaplastic (WHO grade III) ependymomas are among the most common tumors in pediatric patients and have due to frequent recurrences and late relapses a relatively poor outcome. The impact of histopathological grading on patient outcome is controversial and therefore, molecular prognostic and predictive markers are needed to improve patient outcome. To date, the most promising candidate marker is chromosome 1q gain, which has been associated in independent studies with adverse outcome. Furthermore, gene expression and methylation profiles revealed distinct molecular subgroups in the supratentorial and posterior fossa (PF) compartment and Laminin alpha-2 (LAMA2) and Neural Epidermal Growth Factor Like-2 (NELL2) were suggested as surrogate markers for the two PF subgroups PF-EPN-A and PF-EPN-B. PF-EPN-A tumors were also characterized by tenascin-C (TNC) expression and tenascin-C has been suggested as candidate gene on 9q, involved in tumor progression. Therefore, we have analyzed the status of chromosome 1q, TNC, LAMA2, and NELL2 expression in a series of pediatric PF ependymomas in terms of their frequency, associations among themselves, and clinical parameters, as well as their prognostic impact. We confirm the negative prognostic impact of 1q gain and TNC expression and could classify PF ependymomas by these two markers into three molecular subgroups. Tumors with combined 1q gain and TNC expression had the poorest, tumors without 1q gain and TNC expression had a favorable and TNC positive 1q non-gained cases had an intermediate outcome. We found also differences in age and tumor grade in the three subgroups and thus, provide evidence that PF pediatric ependymomas can be divided by chromosome 1q status and TNC expression in three molecular subgroups with distinct clinico-pathological features. These analyses require only few amounts of tumor tissue, are broadly available in the routine clinical neuropathological setting and thus, could be used in further therapy trials to optimize treatment of ependymoma patients.
authors.affiliation: Institute of Neurology, Medical University of Vienna, Vienna, Austria.|Comprehensive Cancer Center, Medical University of Vienna, Währinger Gürtel 18-20, A-1097, Vienna, Austria.|Children's Cancer Research Institute, Vienna, Austria.|Present address: Organ Pathology Unit, School of Medicine, Shimane University, Izumo, Japan.
authors.forename: Asuka
authors.initials: A
authors.lastname: Araki
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria.|Comprehensive Cancer Center, Medical University of Vienna, Währinger Gürtel 18-20, A-1097, Vienna, Austria.
authors.forename: Monika
authors.initials: M
authors.lastname: Chocholous
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria.|Comprehensive Cancer Center, Medical University of Vienna, Währinger Gürtel 18-20, A-1097, Vienna, Austria.
authors.forename: Johannes
authors.initials: J
authors.lastname: Gojo
authors.affiliation: Department of Neurosurgery, Medical University of Vienna, Vienna, Austria.|Comprehensive Cancer Center, Medical University of Vienna, Währinger Gürtel 18-20, A-1097, Vienna, Austria.
authors.forename: Christian
authors.initials: C
authors.lastname: Dorfer
authors.affiliation: Department of Neurosurgery, Medical University of Vienna, Vienna, Austria.|Comprehensive Cancer Center, Medical University of Vienna, Währinger Gürtel 18-20, A-1097, Vienna, Austria.
authors.forename: Thomas
authors.initials: T
authors.lastname: Czech
authors.affiliation: Center for Medical Statistics, Informatics, and Intelligent Systems, Medical University of Vienna, Vienna, Austria.
authors.forename: Harald
authors.initials: H
authors.lastname: Heinzl
authors.affiliation: Department of Radiotherapy, Medical University of Vienna, Vienna, Austria.|Comprehensive Cancer Center, Medical University of Vienna, Währinger Gürtel 18-20, A-1097, Vienna, Austria.
authors.forename: Karin
authors.initials: K
authors.lastname: Dieckmann
authors.affiliation: Children's Cancer Research Institute, Vienna, Austria.
authors.forename: Inge M
authors.initials: IM
authors.lastname: Ambros
authors.affiliation: Children's Cancer Research Institute, Vienna, Austria.
authors.forename: Peter F
authors.initials: PF
authors.lastname: Ambros
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria.|Comprehensive Cancer Center, Medical University of Vienna, Währinger Gürtel 18-20, A-1097, Vienna, Austria.
authors.forename: Irene
authors.initials: I
authors.lastname: Slavc
authors.affiliation: Institute of Neurology, Medical University of Vienna, Vienna, Austria. Christine.haberler@meduniwien.ac.at.|Comprehensive Cancer Center, Medical University of Vienna, Währinger Gürtel 18-20, A-1097, Vienna, Austria. Christine.haberler@meduniwien.ac.at.
authors.forename: Christine
authors.identifier: 0000-0003-1016-0545
authors.initials: C
authors.lastname: Haberler
mesh_terms: D000293:Adolescent; D000367:Age Factors; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D058674:Chromosome Duplication; D002878:Chromosomes, Human, Pair 1; D004806:Ependymoma / Q000145:classification / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D006801:Humans; D007223:Infant; D015192:Infratentorial Neoplasms / Q000145:classification / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D007797:Laminin / Q000378:metabolism; D008297:Male; D060787:Neoplasm Grading; D009419:Nerve Tissue Proteins / Q000378:metabolism; D016019:Survival Analysis; D019063:Tenascin / Q000378:metabolism*; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D007797:Laminin; C104145:NELL2 protein, human; D009419:Nerve Tissue Proteins; D019063:Tenascin; C102645:laminin alpha 2
keywords: Chromosome 1q; Ependymoma; Pediatric; Prognostic markers; Tenascin-C