MGMT Promoter Methylation Status Is Not Related to Histological or Radiological Features in IDH Wild-type Glioblastomas

J Neuropathol Exp Neurol. 2020 Aug 1;79(8):855-862. doi: 10.1093/jnen/nlaa060.

Abstract

O6-methylguanine DNA methyltransferase (MGMT) promoter methylation is an important favorable predictive marker in patients with glioblastoma (GBM). We hypothesized that MGMT status could be a surrogate marker of pretreatment tumor biology observed as histopathological and radiological features. Apart from some radiological studies aiming to noninvasively predict the MGMT status, few studies have investigated relationships between MGMT status and phenotypical tumor biology. We have therefore aimed to investigate such relationships in 85 isocitrate dehydrogenase (IDH) wild-type GBMs. MGMT status was determined by methylation-specific PCR and was assessed for associations with 22 histopathological features, immunohistochemical proliferative index and microvessel density measurements, conventional magnetic resonance imaging characteristics, preoperative speed of tumor growth, and overall survival. None of the investigated histological or radiological features were significantly associated with MGMT status. Methylated MGMT status was a significant independent predictor of improved overall survival. In conclusion, our results suggest that MGMT status is not related to the pretreatment phenotypical biology in IDH wild-type GBMs. Furthermore, our findings suggest the survival benefit of MGMT methylated GBMs is not due to an inherently less aggressive tumor biology, and that conventional magnetic resonance imaging features cannot be used to noninvasively predict the MGMT status.

Keywords: Angiogenesis; Glioblastoma; Histopathology; MGMT promoter methylation; Magnetic resonance imaging; Tumor growth.

MeSH terms

  • Aged
  • Biomarkers, Tumor / genetics
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / pathology*
  • DNA Methylation / genetics
  • DNA Modification Methylases / genetics*
  • DNA Repair Enzymes / genetics*
  • Female
  • Glioblastoma / genetics*
  • Glioblastoma / pathology*
  • Humans
  • Isocitrate Dehydrogenase / genetics
  • Male
  • Middle Aged
  • Promoter Regions, Genetic / genetics
  • Tumor Suppressor Proteins / genetics*

Substances

  • Biomarkers, Tumor
  • Tumor Suppressor Proteins
  • Isocitrate Dehydrogenase
  • DNA Modification Methylases
  • MGMT protein, human
  • DNA Repair Enzymes