Clinicopathological associations and prognostic values of IDH1 gene mutation, MGMT gene promoter methylation, and PD-L1 expressions in high-grade glioma treated with standard treatment

Pan Afr Med J. 2020 Aug 20:36:309. doi: 10.11604/pamj.2020.36.309.24831. eCollection 2020.

Abstract

Introduction: the objective was to evaluate the impact of IDH1 R132H mutation, MGMT methylation and PD-L1 expression in high grade glioma that received standard therapy (surgery, radiation and chemotherapy) to overall survival (OS).

Methods: this is a retrospective study of 35 high grade glioma cases. Genotyping of IDH1 gene alteration on the mutation hotspot R132 (Sanger sequencing method with Applied Biosystems 3500 Genetic Analyzer), EZ DNA Methylation-Gold kit (Zymo Research) is used to study the methylation, Cell line BT549 (ATCC HTB-122) and HCT-116 (ATCC CCL-247) were used as unmethylated control and partially methylated control respectively. Anti-human PD-L1 antibody clone E1L3N®from Cell Signalling Technology (USA) and Rabbit XP®were used to see PDL-1 expression.

Results: anaplastic astrocytoma cases had more MGMT promoter methylation (50%) than glioblastoma multiforme (GBM) (20%), more IDH1 R132H mutation (42%) than GBM (4.3%). Immunohistochemistry tumor proportion score method (TPS) identified 17% and 8.7% were PD-L1 positive in AA and GBM groups, respectively. Cases with IDH1 R132H mutation and MGMT methylation still showed better OS although with high PD-L1 expression.

Conclusion: IDH1 R132H mutation and MGMT methylation were good prognostic markers. High expression of PD-L1 apparently might not indicate poor overall survival in the presence of IDH1 R132 mutation and MGMT methylation.

Keywords: IDH1 mutation; MGMT methylation; PD-L1; anaplastic astrocytoma; glioblastoma multiforme.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Astrocytoma / genetics
  • Astrocytoma / pathology*
  • Astrocytoma / therapy
  • B7-H1 Antigen / genetics*
  • DNA Methylation
  • DNA Modification Methylases / genetics*
  • DNA Repair Enzymes / genetics*
  • Female
  • Glioblastoma / genetics
  • Glioblastoma / pathology*
  • Glioblastoma / therapy
  • Humans
  • Isocitrate Dehydrogenase / genetics*
  • Male
  • Middle Aged
  • Mutation
  • Prognosis
  • Promoter Regions, Genetic / genetics
  • Retrospective Studies
  • Survival Rate
  • Tumor Suppressor Proteins / genetics*
  • Young Adult

Substances

  • B7-H1 Antigen
  • CD274 protein, human
  • Tumor Suppressor Proteins
  • Isocitrate Dehydrogenase
  • IDH1 protein, human
  • DNA Modification Methylases
  • MGMT protein, human
  • DNA Repair Enzymes