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. 2016 Aug 22;4(1):88.
doi: 10.1186/s40478-016-0349-9.

Chromosome 1q gain and tenascin-C expression are candidate markers to define different risk groups in pediatric posterior fossa ependymoma

Asuka Araki  1   2   3   4 , Monika Chocholous  5   2 , Johannes Gojo  5   2 , Christian Dorfer  6   2 , Thomas Czech  6   2 , Harald Heinzl  7 , Karin Dieckmann  8   2 , Inge M Ambros  3 , Peter F Ambros  3 , Irene Slavc  5   2 , Christine Haberler  9   10
Affiliations

Chromosome 1q gain and tenascin-C expression are candidate markers to define different risk groups in pediatric posterior fossa ependymoma

Asuka Araki et al. Acta Neuropathol Commun. .

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.

Keywords: Chromosome 1q; Ependymoma; Pediatric; Prognostic markers; Tenascin-C.

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Figures

Fig. 1
Fig. 1
Histopathology and molecular markers in ependymoma. Classic expendymoma WHO grade II (a); anaplastic ependymoma WHO grade III (b); ependymoma with TNC (c) and LAMA2 (d) expression; ependymoma with (e) and without (f) 1q25 gain (1q25 green fluorochrome, 1p36 red fluorochrome); g, h confirmation of iFSIH results by SNP arrays, Circos plots showing gain of chromosome arm 1q (g) and a balanced copy-number profile (h)
Fig. 2
Fig. 2
Kaplan Meier overall survival curves for chromosome 1q status (a, b), TNC (c, d) and WHO grade (e, f) in the recent (1992–2014; a, c, e) and the entire cohort (1965–2014; b, d, f)
Fig. 3
Fig. 3
Survival probabilities for three molecular subgroups: OS (a) and PFS (b) in the recent cohort (1992–2014) and (c) OS in the entire cohort (1965–2014)
See this image and copyright information in PMC

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