Department of Neurosurgery, Faculty of Medical Sciences, University of Fukui, Yoshida-gun, Fukui, Japan.
Neuropathology. 2009 Aug;29(4):379-88. doi: 10.1111/j.1440-1789.2008.00983.x. Epub 2008 Nov 19.
We studied the expression of O(6)-methylguanine-DNA methyltransferase (O(6)-MGMT), P-glycoprotein (Pgp), and multidrug resistance protein-1 (MRP-1) in 23 glioblastomas using RT-PCR, methylation-specific PCR, and immunohistochemistry, and analyzed their association with overall patient survival. Univariate analysis of collected data demonstrated that the expressions of O(6)-MGMT and MRP-1 detected by immunohistochemistry, in addition to the consistent factors, including preoperative Karnofsky performance scale (KPS), radical surgery, and tumor location and extension, were significant prognostic factors for the overall survival (OS) of patients with glioblastoma, who received nimustine (ACNU)-based chemotherapy in association with surgery and radiotherapy. Among them, following multivariate analysis, preoperative KPS, radical surgery, tumor location, and the expression of O(6)-MGMT remained as significant prognostic factors. These findings suggest that immunohistochemical analysis of O(6)-MGMT in patients with glioblastoma can be a useful method to predict the effects of chemotherapy and identify alternative chemotherapeutic regimens for O(6)-MGMT-positive patients.
我们使用 RT-PCR、甲基化特异性 PCR 和免疫组织化学方法研究了 23 例胶质母细胞瘤中 O(6)-甲基鸟嘌呤-DNA 甲基转移酶 (O(6)-MGMT)、P-糖蛋白 (Pgp) 和多药耐药蛋白 1 (MRP-1) 的表达,并分析了它们与患者总生存的关系。对收集的数据进行单因素分析表明,免疫组织化学检测到的 O(6)-MGMT 和 MRP-1 的表达,除了包括术前卡氏功能状态评分 (KPS)、根治性手术、肿瘤位置和扩展等一致因素外,还是接受尼莫司汀 (ACNU) 为基础的化疗联合手术和放疗的胶质母细胞瘤患者总生存率 (OS) 的显著预后因素。其中,多因素分析后,术前 KPS、根治性手术、肿瘤位置和 O(6)-MGMT 的表达仍然是显著的预后因素。这些发现表明,胶质母细胞瘤患者 O(6)-MGMT 的免疫组织化学分析可以作为预测化疗效果的一种有用方法,并为 O(6)-MGMT 阳性患者确定替代化疗方案。