title: O(6)-methylguanine DNA-methyltransferase methylation status can change between first surgery for newly diagnosed glioblastoma and second surgery for recurrence: clinical implications.
abstract: O(6)-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 > or = 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 > or = 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.
authors.affiliation: Department of Medical Oncology, Azienda USL Bellaria-Maggiore Hospital, Bologna, Italy. alba.brandes@yahoo.it
authors.forename: Alba A
authors.initials: AA
authors.lastname: Brandes
authors.forename: Enrico
authors.initials: E
authors.lastname: Franceschi
authors.forename: Alicia
authors.initials: A
authors.lastname: Tosoni
authors.forename: Stefania
authors.initials: S
authors.lastname: Bartolini
authors.forename: Antonella
authors.initials: A
authors.lastname: Bacci
authors.forename: Raffaele
authors.initials: R
authors.lastname: Agati
authors.forename: Claudio
authors.initials: C
authors.lastname: Ghimenton
authors.forename: Sergio
authors.initials: S
authors.lastname: Turazzi
authors.forename: Andrea
authors.initials: A
authors.lastname: Talacchi
authors.forename: Miran
authors.initials: M
authors.lastname: Skrap
authors.forename: Gianluca
authors.initials: G
authors.lastname: Marucci
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Volpin
authors.forename: Luca
authors.initials: L
authors.lastname: Morandi
authors.forename: Stefano
authors.initials: S
authors.lastname: Pizzolitto
authors.forename: Marina
authors.initials: M
authors.lastname: Gardiman
authors.forename: Alvaro
authors.initials: A
authors.lastname: Andreoli
authors.forename: Fabio
authors.initials: F
authors.lastname: Calbucci
authors.forename: Mario
authors.initials: M
authors.lastname: Ermani
mesh_terms: D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000235:genetics* / Q000401:mortality / Q000601:surgery; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000235:genetics*; D045643:DNA Repair Enzymes / Q000235:genetics*; D005260:Female; D005909:Glioblastoma / Q000235:genetics* / Q000401:mortality / Q000601:surgery; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000601:surgery; D011379:Prognosis; D011401:Promoter Regions, Genetic; D012189:Retrospective Studies; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D025521:Tumor Suppressor Proteins; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes