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Original article
Correlation of the quantitative level of MGMT promoter methylation and overall survival in primary diagnosed glioblastomas using the quantitative MethyQESD method
  1. Charlotte von Rosenstiel1,
  2. Benedikt Wiestler2,
  3. Bernhard Haller3,
  4. Friederike Schmidt-Graf4,
  5. Jens Gempt5,
  6. Marcus Bettstetter6,
  7. Laura Rihani1,
  8. Wei Wu1,
  9. Bernhard Meyer5,
  10. Jürgen Schlegel1,
  11. Friederike Liesche-Starnecker1
  1. 1Department of Neuropathology, Institute of Pathology, Technical University Munich, School of Medicine, Munich, Germany
  2. 2Department of Diagnostic and Interventional Neuroradiology, Klinikum rechts der Isar, Technical University Munich, School of Medicine, Munich, Germany
  3. 3Institute of Medical Informatics, Technical University Munich, School of Medicine, Munich, Germany
  4. 4Department of Neurology, Klinikum rechts der Isar, Technical University Munich, School of Medicine, Munich, Germany
  5. 5Department of Neurosurgery, Klinikum rechts der Isar, Technical University Munich, School of Medicine, Munich, Germany
  6. 6Teilgemeinschaftspraxis Molekularpathologie Südbayern, Munich, Germany
  1. Correspondence to Dr. Friederike Liesche-Starnecker, Department of Neuropathology, Institute of Pathology, Technical University Munich, School of Medicine, Munich, Germany; friederike.liesche{at}tum.de

Abstract

Aims O(6)-methylguanine-DNA-methyltransferase (MGMT) promoter methylation is a high predictive factor for therapy results of temozolomide in patients with glioma. The objective of this work was to analyse the impact of MGMT promoter methylation in patients with primary diagnosed glioblastoma (GBM) relating to survival using a quantitative method (methylation quantification of endonuclease-resistant DNA, MethyQESD) by verifying a cut-off point for MGMT methylation provided by the literature (</≥10%) and calculating an optimal cut-off.

Methods 67 patients aged 70 years or younger, operated between January 2013 and December 2015, with newly diagnosed IDH wild-type GBM and clinical follow-up were retrospectively investigated in this study. A known MGMT promoter methylation status was the inclusion criteria.

Results Median overall survival (OS) was 16.9 months. Patients who had a methylated MGMT promoter region of ≥10% had an improved OS compared with patients with a methylated promoter region of <10% (p=0.002). Optimal cut-off point for MGMT promoter methylation was 11.7% (p=0.012).

Conclusion The results confirm that the quantitative level of MGMT promoter methylation is a positive prognostic factor in newly diagnosed patients with GBM. The cut-off provided by the literature (</≥10%) and the calculated optimal cut-off value of 11.7% give a statistically significant separation. Hence, MethyQESD is a reliable method to calculate MGMT promoter methylation in GBM.

  • glioblastoma
  • glioma
  • brain tumour
  • molecular pathology
  • predictive marker
  • overall survival
  • promoter methylation
  • MGMT
  • MethyQESD

https://doi.org/10.1136/jclinpath-2019-206104

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    Footnotes

    • Handling editor Prof Runjan Chetty.

    • Contributors CvR, FL and JS conceived and designed the study. JS, FL, FSG, BM and JG made data available. CvR, BW and BH analysed the data. MB gave technical advice regarding the MethyQESD method. CvR drafted the first version of the manuscript. CvR, FL, BW, BH, FSG, JG, LR, WW, BM, MB and JS interpreted the results, edited, substantively revised and approved the final manuscript.

    • Funding statement The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

    • Competing interests None declared.

    • Patient consent for publication Not required.

    • Provenance and peer review Not commissioned; internally peer reviewed.

    • Data availability statement Data are available on reasonable request.