Correlation of the quantitative level of MGMT promoter methylation and overall survival in primary diagnosed glioblastomas using the quantitative MethyQESD method

J Clin Pathol. 2020 Feb;73(2):112-115. doi: 10.1136/jclinpath-2019-206104. Epub 2019 Aug 17.

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.

Keywords: MGMT; MethyQESD; brain tumour; glioblastoma; glioma; molecular pathology; overall survival; predictive marker; promoter methylation.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents, Alkylating / therapeutic use
  • Biomarkers, Tumor / genetics*
  • Brain Neoplasms / drug therapy
  • Brain Neoplasms / enzymology
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / mortality
  • DNA Methylation*
  • DNA Modification Methylases / genetics*
  • DNA Repair Enzymes / genetics*
  • Female
  • Glioblastoma / drug therapy
  • Glioblastoma / enzymology
  • Glioblastoma / genetics*
  • Glioblastoma / mortality
  • Humans
  • Male
  • Middle Aged
  • Prognosis
  • Promoter Regions, Genetic*
  • Retrospective Studies
  • Risk Factors
  • Temozolomide / therapeutic use
  • Time Factors
  • Tumor Suppressor Proteins / genetics*

Substances

  • Antineoplastic Agents, Alkylating
  • Biomarkers, Tumor
  • Tumor Suppressor Proteins
  • DNA Modification Methylases
  • MGMT protein, human
  • DNA Repair Enzymes
  • Temozolomide