BACKGROUND: O(6) -methylguanine-DNA methyltransferase (MGMT) promoter 
methylation status was proposed as a prognostic biomarker for patients with 
glioblastoma. However, the prognostic impact of MGMT in patients with newly 
diagnosed glioblastoma who receive carmustine-releasing wafers (Gliadel) along 
with temozolomide (TMZ) is still unknown.
METHODS: MGMT promoter methylation status and protein expression were analyzed 
in formalin-fixed, paraffin-embedded tumor specimens obtained from 111 French 
patients with newly diagnosed glioblastoma. Patients received the Gliadel wafers 
followed by radiotherapy plus concomitant and adjuvant TMZ chemotherapy while 
they were enrolled in a French multicenter prospective study.
RESULTS: For the whole cohort, the median overall survival (OS) was 17.5 months, 
and the progression-free survival was 10.3 months. Patients with tumors that 
harbored MGMT methylation had a significantly longer OS compared with patients 
who had wild-type MGMT (21.7 months vs 15.1 months; P = .025). Similarly, 
patients who had low MGMT protein expression (≤15%) had a significantly improved 
OS compared with patients who had high MGMT expression (27.0 months vs 15.1 
months; P = .021). The extent of resection was the strongest clinical predictor 
of outcome. In multivariate Cox models that were adjusted for sex, performance 
status, and extent of surgery, both MGMT methylation and protein expression were 
identified as independent prognosticators, and the finding was validated 
internally using a bootstrap resampling technique. Discrepancies were identified 
between protein expression and MGMT methylation status, thus suggesting that the 
2 assays probably assess different biologic features.
CONCLUSIONS: MGMT promoter methylation status and low MGMT expression both were 
identified as positive prognosticators in patients with newly diagnosed 
glioblastoma who underwent surgical resection and received Gliadel wafer 
implants followed by adjuvant radiotherapy and concomitant oral TMZ chemotherapy 
(the Stupp protocol).