O6-Methylguanine DNA methyltransferase expression in tumor cells predicts outcome of radiotherapy plus concomitant and adjuvant temozolomide therapy in patients with primary glioblastoma

• DOI: 10.1007/s10014-011-0022-8
• Publication Date: 2011-02-17T15:53:42Z
• Authors: Reiko Watanabe; Yoko Nakasu; Hiroshi Tashiro; Koichi Mitsuya; Ichiro Ito; Satoshi Nakasu; Takashi Nakajima
• Keywords: Adult; Male; Brain Neoplasms; Middle Aged; Combined Modality Therapy; Disease-Free Survival; Gene Expression Regulation, Enzymologic; 3. Good health; Dacarbazine; Gene Expression Regulation, Neoplastic; O(6)-Methylguanine-DNA Methyltransferase; 03 medical and health sciences; Treatment Outcome; 0302 clinical medicine; Cell Line, Tumor; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Temozolomide; Humans; Female; Glioblastoma; Antineoplastic Agents, Alkylating; Retrospective Studies

Expression of the O(6)-methylguanine-DNA methyltransferase (MGMT) gene has been shown to correlate with clinical outcomes in patients with glioblastoma multiforme treated with alkylating agents. We evaluated MGMT protein expression in 53 primary glioblastomas by the immunohistochemistry (IHC) and analyzed the correlation between results of immunostaining and patient outcomes. There were 28 MGMT-immunopositive and 25 negative glioblastomas. Patients with MGMT-immunonegative glioblastomas showed significantly longer progression-free survival (PFS) (P = 0.0032), but no statistically significant benefits on overall survival (OS) (P = 0.0825) were shown. In 41 glioblastomas treated with temozolomide (TMZ) therapy (MGMT-immunopositive: n = 22, negative: n = 19), both PFS and OS were significantly better in MGMT-immunonegative glioblastomas. (PFS: P = 0.0015, OS: P = 0.0384). We conclude that MGMT expression on immunohistochemistry (IHC) correlates with outcomes in patients with primary glioblastoma receiving TMZ and suggest the use of MGMT-IHC as a surrogate marker for predicting tumor chemosensitivity.