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

Author:

Mikkelsen Vilde Elisabeth1ORCID,Dai Hong Yan2,Stensjøen Anne Line3,Berntsen Erik Magnus34ORCID,Salvesen Øyvind5,Solheim Ole67ORCID,Torp Sverre Helge12ORCID

Affiliation:

1. From the Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, NTNU—Norwegian University of Science and Technology

2. Department of Pathology, St Olav’s University Hospital

3. Department of Circulation and Medical Imaging, Faculty of Medicine and Health Sciences, NTNU—Norwegian University of Science and Technology

4. Department of Radiology and Nuclear Medicine, St. Olav’s University Hospital

5. Department of Public Health and Nursing

6. Department of Neuromedicine and Movement Science, Faculty of Medicine and Health Sciences, NTNU—Norwegian University of Science and Technology

7. Department of Neurosurgery, St. Olav’s University Hospital, Trondheim, Norway

Abstract

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.

Funder

NTNU-Norwegian University of Science and Technology

National Competence Centre for Ultrasound and Image Guided Therapy

Central Norwegian Brain Tumor Registry

National Advisory Committee on Treatment Guidelines for Brain Tumors

Publisher

Oxford University Press (OUP)

Subject

Cellular and Molecular Neuroscience,Neurology (clinical),Neurology,General Medicine,Pathology and Forensic Medicine

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