O6-methylguanine DNA-methyltransferase methylation status can change between first surgery for newly diagnosed glioblastoma and second surgery for recurrence: Clinical implications

Alba A. Brandes, Enrico Franceschi, Alicia Tosoni, Stefania Bartolini, Antonella Bacci, Raffaele Agati, Claudio Ghimenton, Sergio Turazzi, Andrea Talacchi, Miran Skrap, Gianluca Marucci, Lorenzo Volpin, Luca Morandi, Stefano Pizzolitto, Marina Gardiman, Alvaro Andreoli, Fabio Calbucci, Mario Ermani

Research output: Contribution to journalArticlepeer-review

Abstract

O6-methylguanine DNA-methyltransferase (MGMT) promoter methylation status is a prognostic factor in newly diagnosed glioblastoma patients. However, it is not yet clear whether, and if so how, MGMT methylation status may change. Moreover, it is unknown whether the prognostic role of this epigenetic feature is retained during the disease course. A retrospective analysis was made using a database of 614 glioblastoma patients treated prospectively from January 2000 to August 2008. We evaluated only patients who met the following inclusion criteria: age ≥ 18 years; performance status 0-2; histological diagnosis of glioblastoma at both first and second surgery for recurrence; postoperative treatment consisting of: (i) radiotherapy (RT) followed by adjuvant temozolomide (TMZ) until 2005 and (ii) TMZ concurrent with and adjuvant to RT after 2005; a time interval ≥3 months between first and second surgery. MGMT status was evaluated at first and second surgery in all 44 patients (M:F 32:12, median age: 49 years, range: 27-67 years). In 38 patients (86.4%), MGMT promoter status was assessable at both first and second surgery. MGMT methylation status, changed in 14 patients (37%) of second surgery samples and more frequently in methylated than in unmethylated patients (61.5% vs 24%, P = .03). The median survival was significantly influenced only by MGMT methylation status determined at first surgery (P = .04). Significant changes in MGMT methylation status during the course of GBM occur more frequently in MGMT methylated than unmethylated cases. MGMT methylation status determined at first surgery appears to be of prognostic value; however, it is not predictive of outcome following second surgery.

Original languageEnglish
Pages (from-to)283-288
Number of pages6
JournalNeuro-Oncology
Volume12
Issue number3
DOIs
Publication statusPublished - Mar 2010

Keywords

  • Glioblastoma
  • MGMT
  • Recurrence
  • Second surgery
  • Temozolomide

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Clinical Neurology

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