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.
Highlights
Ependymomas are neuroepithelial tumors, which arise throughout the neuraxis and are usually associated with the ventricular cavities or the spinal central canal
Outcome of pediatric patients with intracranial ependymoma remains relatively poor with 5-year progression free survival rates between 30 % and 69.1 % and 5 year overall survival rates between 60 and 81 % in different age groups and therapeutic trial cohorts [4,5,6,7]
Lama2 expression was detectable in 88.5 % and 53.8 % of the tumors, respectively
Summary
Ependymomas are neuroepithelial tumors, which arise throughout the neuraxis and are usually associated with the ventricular cavities or the spinal central canal. They are considered to originate from radial glial stem cells [1] and may occur at any age. Data on the prognostic impact of tumor grade i.e. classic versus anaplastic on patient outcome are controversial. The biological behavior of ependymomas WHO grade II and III is still poorly predictable, and there is a need for robust molecular prognostic and predictive markers to optimize treatment strategies and improve patient outcome
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