Prognostic Significance of MGMT Promoter Methylation in Patients with Glioblastoma Undergoing Surgical Intervention: A Retrospective Study in Northeastern Iran

Anvari, Kazem; Seilanian Toussi, Mehdi; Ayatollahi, Hossein; Bahadorkhan, Gholamreza; Ghavam Nasiri, Mohammadreza; Fazl Ersi, Mitra

doi:10.30476/mejc.2018.42120

Prognostic Significance of MGMT Promoter Methylation in Patients with Glioblastoma Undergoing Surgical Intervention: A Retrospective Study in Northeastern Iran

Document Type : Original Article(s)

Authors

Kazem Anvari ¹

Mehdi Seilanian Toussi ¹

Hossein Ayatollahi ²

Gholamreza Bahadorkhan ³

Mohammadreza Ghavam Nasiri ¹

Mitra Fazl Ersi ¹

¹ Cancer Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

² Cancer Molecular Pathology Research Center, Ghaem Hospital, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

³ Department of Neurosurgery, Ghaem Hospital, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

https://doi.org/10.30476/mejc.2018.42120

Abstract

Background: The standard of care for glioblastoma is concurrent chemoradiotherapy and adjuvant chemotherapy with Temozolomide. In this trial, we have investigated the impact of MGMT promoter methylation on prognosis and benefit from Temozolomide based chemotherapy in a group of patients with glioblastoma in our region.Methods: This retrospective study included glioblastoma patients treated in our institute between 2006 and 2011. We used methylation specific PCR to detect methylation in the promoter region of the MGMT gene. The Kaplan-Meier technique was used to calculate overall survival from the time of diagnosis to the time of death. We utilized the log-rank test and Cox-regression model for univariate and multivariate analyses of potential prognostic factors.Results: There were 78 patient participants with a median age of 50 (range: 20 to 75) years and a male to female ratio of 56/22. All patients underwent minimal surgical resection which was considered as a biopsy. All patients received adjuvant radiotherapy with a median dose of 60 Gy (54-60 Gy) and 25 patients received concomitant Temozolomide. The MGMT promoter methylation was found in 19 (24.4%) patients and was relatively more frequent in men (28.6%) compared to women (13.6%; P=0.16).This genetic change was associated with a significantly higher 2-year survival in men (57.2%) compared to women (16.8%; P<0.001). Multivariate analysis indicated that male sex and MGMT promoter methylation were independently associated with more favorable prognosis.Conclusion: In our series, MGMT promoter methylation was a significant independent prognostic factor. The finding of sex as an independent prognostic factor would need further validation.