Department of Neurosurgery, Chonnam National University Hwasun Hospital, Gwangju, Republic of Korea.
Oncol Rep. 2010 May;23(5):1269-76. doi: 10.3892/or_00000760.
The aim of this study was to evaluate variations of O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation and protein expression after adjuvant treatment in glioblastoma patients. Sixteen patients with a glioblastoma underwent 34 microsurgeries including 18 re-operations. After surgery, patients underwent follow-up with radiotherapy and chemotherapy (temozolomide, ACNU and cisplatin) between 2000 and 2008. To investigate MGMT methylation and MGMT expression, methylation-specific PCR (MSP) and immunohistochemical staining (IHC) were performed. The methylation status of the MGMT promoter was altered in five (27.8%) of 18 re-operation specimens. In four specimens, the MGMT promoter was found to be methylated after primary surgery, but was found to be unmethylated on post-treatment samples. MGMT protein expression was altered in 15 (83.3%) of 18 cases. Fifteen specimens showed higher levels of protein expression as compared to previous samples and three samples demonstrated a similar expression pattern. After irradiation and exposure to steroid and temozolomide 6 and 24 h later, a methylated MGMT promoter and negative protein expression were seen in U343 glioblastoma cell lines which have methylated promoter and negative protein expression. Variations in MGMT promoter methylation and protein expression can occur after treatment. We suggest that changes of MGMT promoter methylation and protein expression might not be related to a direct effect of irradiation and exposure to steroid and temozolomide.
本研究旨在评估胶质母细胞瘤患者在辅助治疗后 O6-甲基鸟嘌呤-DNA 甲基转移酶（MGMT）启动子甲基化和蛋白表达的变化。16 名胶质母细胞瘤患者接受了 34 次微创手术，其中 18 次为再次手术。手术后，患者于 2000 年至 2008 年间接受了放疗和化疗（替莫唑胺、ACNU 和顺铂）的随访。为了研究 MGMT 甲基化和 MGMT 表达，进行了甲基化特异性 PCR（MSP）和免疫组织化学染色（IHC）。在 18 个再次手术标本中，有 5 个（27.8%）的 MGMT 启动子甲基化状态发生了改变。在 4 个标本中，MGMT 启动子在初次手术后被发现甲基化，但在治疗后样本中被发现是非甲基化的。在 18 例中，有 15 例（83.3%）MGMT 蛋白表达发生了改变。与之前的样本相比，15 个标本的蛋白表达水平升高，3 个标本表现出相似的表达模式。在 U343 胶质母细胞瘤细胞系中，MGMT 启动子在接受照射和暴露于类固醇和替莫唑胺 6 和 24 小时后发生甲基化，且蛋白表达为阴性，这些细胞系的 MGMT 启动子为甲基化且蛋白表达为阴性。MGMT 启动子甲基化和蛋白表达在治疗后可能发生变化。我们认为，MGMT 启动子甲基化和蛋白表达的变化可能与照射、暴露于类固醇和替莫唑胺的直接作用无关。
