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EGFR Methylation in Meningioma is Significantly Associated with Higher Tumor Grade and Reduced Progression-Free Survival

Friday, May 3, 2024

Presenting Author(s)

Gabrielle Hovis, BS

Medical Student
Department of Neurosurgery, University of California, Los Angeles
Flagstaff, AZ, US

Co-Author(s)

RE

Richard G. Everson, MD

Assistant Professor
Departments of Neurosurgery, Radiation Oncology, Head and Neck Surgery, Jonsson Comprehensive Cancer Center, Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Los Angeles, CA
Los Angeles, California, United States
MM

Mahlet Mekonnen, BS

Postgraduate Researcher
Department of Neurosurgery, University of California, Los Angeles
Los Angeles, CA, US
BU

Benjamin Uy, MD, PhD (he/him/his)

Neurosurgery Resident
Department of Neurosurgery, University of California, Los Angeles
Los Angeles, California, United States
MW

Madhuri Wadehra, PhD

Adjunct Assistant Professor
Department of Pathology and Laboratory Medicine, University of California, Los Angeles, United States
Isaac Yang, MD (he/him/his)

Professor of Neurosurgery
Departments of Neurosurgery, Radiation Oncology, Head and Neck Surgery, Jonsson Comprehensive Cancer Center, Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, Los Angeles, CA
Los Angeles, California, United States

Introduction: Meningioma accounts for over one third of all primary central nervous system lesions. Molecular profiling and epigenetic modifications provide valuable insight into the mechanisms of tumor growth and invasion. The overexpression of the epidermal growth factor receptor (EGFR) in meningioma is suggestive of its role in tumorigenesis. This study assesses the prognostic value of EGFR promoter methylation in meningioma.

Methods: DNA was extracted from primary tumor samples using standardized proteinase K digestion followed by phenol/chloroform extractions. EGFR methylation status was analyzed using methylation-specific polymerase chain reaction (PCR). PCR was carried out using a DNA-workstation L020 GC (Kisker, Steinfurt, Germany).

Results: The mean age at diagnosis was 44 years (range: 21-75 years) and 64% of the patients were female. The median follow-up was 29.4 months (range: 0.1-83.0 months). Recurrence was seen in 36% of patients and the corresponding median progression-free survival (PFS) was 12.4 months (range: 1.6-52.3 months). Gross total resection was performed in 64% of patients and 48% received adjuvant radiation therapy. EGFR promoter methylation was found in 68% of tumors. Progression was noted in 28.6% of World Health Organization (WHO) grade I tumors, 71.4% of grade II tumors, and 66.7% of grade III tumors. PFS was significantly shorter in patients with EGFR promoter methylation compared to their non-EGFR methylation counterparts (median PFS: 12.5 vs 36.1 months, p=0.02). All tumors that displayed progression exhibited EGFR promoter methylation, suggesting involvement of EGFR methylation in tumor recurrence.

Conclusion : These results demonstrate that EGFR promoter methylation is associated with higher tumor grade and poorer PFS. EGFR promoter methylation may be an important biomarker for the prediction of recurrence in meningioma. Future multicenter studies are warranted to further elucidate these conclusions.