Impact of MGMT methylation status on 1p/19q intact anaplastic gliomas

Background: Chromosomes 1p/19q codeletion has been recognized as a prognostic and predictive factor in patients (pts) with grade 3 gliomas. Non-codeleted (intact) anaplastic oligodendroglioma showed a survival comparable to that usually observed in pts with anaplastic astrocytomas; MGMT methylation status, moreover, has been found to be a prognostic factor in glioblastoma and anaplastic gliomas (AG). Methods: A retrospective analysis was made using a database of 253 AG pts followed prospectively between January 1998 and August 2008. We evaluated only pts who met the following inclusion criteria: age ≥ 18 years; PS 0-2; histological diagnosis of AG with 1p/19q intact, as determined by FISH analysis; treatment with postoperative radiotherapy (RT) and chemotherapy (CT); MGMT status determined using methylation specific PCR. The study aim was to evaluate the role of MGMT methylation status in 1p/19q codeleted AG pts. The log-rank test was used to evaluate the significance of the prognostic variables. Results: 67 pts (m/f: 35/32, median age: 41.3 years, range: 18-70 years) were enrolled. Histology was anaplastic oligodendroglioma in 17 pts, anaplastic oligoastrocytoma in 20 pts, and anaplastic astrocytoma in 30 pts; all these pts were 1p19q intact and received surgery, RT, and CT. MGMT status, assessable in 58 pts (86.6%), was methylated in 33 pts (56.9%), and unmethylated in 25 pts (43.1%). Median progression-free survival (PFS) was 32.3 months (95%CI: 9.9-54.7). No enhancement at time of diagnosis (p = 0.003), gross total resection (p = 0.03), age (p = 0.001), and MGMT methylation (p = 0.05) were significantly correlated with better PFS. Median survival was 65.2 months (95% CI: 45-85.3). Only age (p = 0.001) and KPS (p = 0.02) correlated with a better survival. Conclusions: MGMT methylation status may provide adjunctive prognostic information in pts with 1p/19q intact AG, indicating a prolonged PFS in pts harboring MGMT promoter methylation.