Anti-O6-methylguanine-methyltransferase (MGMT) immunohistochemistry in glioblastoma multiforme: Observer variability and lack of association with patient survival impede its use as clinical biomarker

Matthias Preusser, Robert Charles Janzer, Jörg Felsberg, Guido Reifenberger, Marie France Hamou, Annie Claire Diserens, Roger Stupp, Thierry Gorlia, Christine Marosi, Harald Heinzl, Johannes A. Hainfellner, Monika Hegi

Research output: Contribution to journalArticlepeer-review

184 Scopus citations

Abstract

Silencing of O6-methylguanine-DNA methyltransferase (MGMT) protein expression because of MGMT gene promoter hypermethylation is considered to be associated with postoperative chemoradiotherapy benefits in glioblastoma multiforme (GBM) patients. The objective of this study was to clarify the usability of MGMT immunohistochemistry (IHC) as a clinical biomarker. We immunostained a tissue microarray containing biopsy samples of 164 GBM patients from the European Organization for Research and Treatment of Cancer and the National Cancer Institute of Canada (EORTC/NCIC) trial 26981/22981 using two commercial anti-MGMT antibodies (clones MT3.1 and MT23.2). Immunostaining results were semiquantitatively evaluated by four observers from three neuropathological laboratories using a predefined algorithm. We analyzed (i) inter- and intraobserver agreement on MGMT expression (kappa statistics); (ii) correlation of MGMT expression with MGMT promoter methylation status (kappa statistics); and (iii) correlation of MGMT expression with patient outcome (log-rank test). Interobserver agreement on MGMT expression varied from slight to almost perfect, whereas intraobserver agreement ranged from substantial to almost perfect. MGMT expression showed poor to moderate correlation with MGMT promoter methylation status. We found no significant association of MGMT expression with patient outcome. In our hands, observer variability as well as lack of association with the MGMT promoter methylation status and patient survival impeded the use of anti-MGMT immunohistochemistry as a clinical biomarker for routine diagnostic purposes.

Original languageEnglish (US)
Pages (from-to)520-532
Number of pages13
JournalBrain Pathology
Volume18
Issue number4
DOIs
StatePublished - Oct 2008

Keywords

  • Biomarker
  • Glioblastoma
  • Immunohistochemistry
  • MGMT
  • Prognosis

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neuroscience(all)
  • Clinical Neurology

Fingerprint

Dive into the research topics of 'Anti-O6-methylguanine-methyltransferase (MGMT) immunohistochemistry in glioblastoma multiforme: Observer variability and lack of association with patient survival impede its use as clinical biomarker'. Together they form a unique fingerprint.

Cite this