O(6)-Methylguanine DNA methyltransferase (MGMT) is implicated as a major predictive factor for treatment response to
alkylating agents including
temozolomide (TMZ) of
glioblastoma multiforme (GBM) patients. However, whether the MGMT status in GBM patients should be detected at the level of promoter methylation or
protein expression is still a matter of debate. Here, we compared promoter methylation (by methylation-specific polymerase chain reaction) and
protein expression (by Western blot) in
tumor cell explants with respect to prediction of TMZ response and survival of GBM patients (n = 71). Methylated MGMT gene promoter sequences were detected in 47 of 71 (66%) cases, whereas 37 of 71 (52%) samples were scored positive for MGMT
protein expression. Although overall promoter methylation correlated significantly with
protein expression (chi(2) test, P < .001), a small subgroup of samples did not follow this association. In the multivariate Cox regression model, a significant interaction between MGMT
protein expression, but not promoter methylation, and TMZ
therapy was observed (test for interaction, P = .015). In patients treated with TMZ (n = 42), MGMT
protein expression predicted a significantly shorter overall survival (OS; hazard ratio [HR] for death 5.53, 95% confidence interval [CI] 1.76-17.37; P = .003), whereas in patients without TMZ
therapy (n = 29), no differences in OS were observed (HR for death 1.00, 95% CI 0.45-2.20; P = .99). These data suggest that lack of MGMT
protein expression is superior to promoter methylation as a predictive marker for TMZ response in GBM patients.