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

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Where lies the threshold level of MGMT promotor hypermethylation in malignant gliomas

Meeting Abstract

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  • Julia Sophie Onken - Neurosurgery Charité Berlin, Berlin, Deutschland
  • Koll Randi - Neuropathology Charité Berlin, Berlin, Deutschland
  • Paschereit Fabienne - Berlin , Deutschland
  • Patsouris Victor - Neurosurgery Charité Berlin, Berlin, Deutschland
  • Vajkoczy Peter - Neurosurgery Charité Berlin, Berlin, Deutschland
  • Heppner Frank - Neuropathology Charité Berlin, Berlin, Deutschland
  • Radke Josefine - Neuropathology Charité Berlin, Berlin, 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. DocMi.22.07

doi: 10.3205/17dgnc518, urn:nbn:de:0183-17dgnc5183

Published: June 9, 2017

© 2017 Onken 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: Hypermethylation of the O6-methylguanine-DNA methyltransferase (MGMT) promotor is associated with improved treatment response and prolonged survival in glioma patients. Pyrosequencing is an approved method to determine MGMT promotor status, but still adequate threshold levels for clinical decision making need to be determined on the basis of a well-defined patient cohort.

Methods: This study included 263 newly diagnosed, previously untreated, IDH R132 wildtype malignant gliomas with the histopathological morphology of a glioblastoma multiforme WHO grade IV. IDH R132 Status was assessed with immunohistochemistry (IHC). The MGMT promoter methylation status was evaluated with methylation-specific polymerase chain reaction (MSP) and pyrosequencing (PSQ). Overall survival was correlated to percent MGMT promotor methylation.

Results: The patient population was well balanced in concerns of age, extend of surgical resection and adjuvant therapy. Patients with a KPS less than 70% were excluded from the study. The degree of MGMT promotor and GpG (GpG1-5) island methylation was independent of age and tumor localization. Statistical analysis revealed a threshold of 15-20% MGMT promotor methylation, which was associated with significant difference in survival (median survival 13 month vs. 25 month, p*=0.01, HR 1.915, 95% confidence interval 1.162 to 3.155)

Conclusion: Here we report that a reasonable threshold level of MGMT promotor methylation lies above 15-20% predicting survival benefit and therapy response. Among the investigated CpG islands CpG3 and CpG5 are the main contributors to favorable outcome. Further RCT studies need to approve the cut-off value on the basis for future treatment decisions.