gms | German Medical Science

68th Annual Meeting of the German Society of Neurosurgery (DGNC)
7th Joint Meeting with the British Neurosurgical Society (SBNS)

German Society of Neurosurgery (DGNC)

14 - 17 May 2017, Magdeburg

Implications of Notch signaling in pediatric high grade glioma

Meeting Abstract

  • Daniela Pierscianek - Department of Neurosurgery, Essen, Deutschland
  • Oliver M. Müller - Universitätsklinikum Essen der Universität Duisburg-Essen, Klinik und Poliklinik für Neurochirurgie, Essen, Deutschland
  • Yahya Ahmadipour - Klinik für Neurochirurgie, Universitätsklinikum Essen, Essen, Deutschland
  • Yuan Zhu - Essen, Deutschland
  • Ulrich Sure - Universitätsklinikum Essen der Universität Duisburg-Essen, Klinik und Poliklinik für Neurochirurgie, Essen, Deutschland
  • Nicolai El Hindy - Universitätsklinikum Essen der Universität Duisburg-Essen, Klinik und Poliklinik für Neurochirurgie, Essen, Deutschland

Deutsche Gesellschaft für Neurochirurgie. Society of British Neurological Surgeons. 68. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), 7. Joint Meeting mit der Society of British Neurological Surgeons (SBNS). Magdeburg, 14.-17.05.2017. Düsseldorf: German Medical Science GMS Publishing House; 2017. DocDI.07.05

doi: 10.3205/17dgnc220, urn:nbn:de:0183-17dgnc2207

Published: June 9, 2017

© 2017 Pierscianek et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. See license information at http://creativecommons.org/licenses/by/4.0/.


Outline

Text

Objective: Malignant glioma (MG) are highly aggressive brain tumors, characterized by massive neovascularization, necrosis and therapy resistance. Many investigations report marked differences between adult and pediatric MG. Deregulated Notch signaling has been associated to different malignancies, comprising primary adult glioblastoma (GBM). Hitherto pediatric MG have not been investigated for deregulated Notch signaling. Hence our investigation aimed to reveal implications of Notch signaling in pediatric HG.

Methods: All children (age <=16 years) operated for MG in our department from 2008 to 2015 were included. Basic clinical parameters like age, gender, infra- and supratentorial location were assessed. Major components of Notch signaling (receptor: Notch1, Notch4; ligand: Dll4, Jagged1; effector: Hey1, Hey2) were examined by real-time reverse-transcription-polymerase chain reaction (PCR) and Western blotting (WB) in these children and compared to adult GBM (n=26) and control (n=11) brain tissue. Vascular pattern (VP) was analyzed after vessel staining with laminin.

Results: 12 children (5 boys, 7 girls) with a median age of 9.7 years were included. 4 (33%) children had a MG °III and 8 (67%) a MG °IV. The mRNA levels of Dll4, Jagged1, Notch1, Notch4, Hey1 and Hey2 were 55.7-, 13.3-, 2.2-, 138.6-, 7.9-, and 24.7-fold elevated, respectively, in pediatric MG, compared to control. Interestingly, the comparison of pediatric and adult MG revealed significant differences only for Dll4 (p=0.016) and Notch4 (p=0.015), implicated in angiogenesis. WB confirmed marked protein expression of Dll4 in pediatric cases (4.5 fold, p=0.002) and no significant difference between Notch1 protein expression compared to adult cases. There was no difference in mRNA expression between MG°III/°IV, as well as infra-/supratentorial location. Laminin staining revealed predominantly classic, effective vascularization pattern in pediatric MG.

Conclusion: According to our results, pediatric MG are different in comparison to adult MG. Major Notch signaling components are extremely upregulated in pediatric cases. Main differences in comparison to adult MG are upregulation of DLL4 and Notch4, which affect vascularization pattern. Further investigations are necessary to correlate our finding with clinical parameters, especially survival.