Prognostic significance of loss of O6-methylguanine-DNA methyltransferase expression in supratentorial diffuse low-grade astrocytoma
Prognostic significance of loss of O6-methylguanine-DNA methyltransferase expression in supratentorial diffuse low-grade astrocytoma
复制标题
DOI：
10.1016/j.surneu.2006.12.053
复制
发表时间：
2007-12-01
影响因子：
--
通讯作者：
Matsuda, Masayuki
中科院分区：
文献类型：
--
作者：
Nakasu, Satoshi;Fukami, Tadateru;Matsuda, Masayuki
背景：O-6-甲基鸟嘌呤-DNA甲基转移酶是一种DNA修复蛋白。MGMT基因启动子甲基化导致的表观遗传沉默被认为是致癌的重要因素。方法：应用免疫组化方法检测28例幕上弥漫性星形细胞瘤中MGMT的表达。MGMT表达、增殖指数（MIB-1）和各种临床因素的预后意义进行了评估。结果：19例MGMT阳性和9例MGMT阴性星形细胞瘤。5年恶变率分别为12.3%和51.4%。在单变量（P = 0.004）和多变量分析（P = 0.044）中差异显著。年龄、性别、手术范围、MIB-1值和初始治疗时的放射治疗与恶性进展无关。10年总生存率分别为71.8%和58.3%的患者与MGMT阳性和MGMT阴性肿瘤，这两组之间没有显着差异（P = 0.079）。两名长期生存的MGMT阴性肿瘤患者对亚硝基脲类药物化疗反应良好，恶性转化后存活超过8年。在单变量分析中，患者的年龄（P = 0.0047）和手术切除程度（P = 0.0082）影响总生存率。结论：MGMT的表达状态对总生存期无影响，但免疫组化检测MGMT的表达可能是判断肿瘤进展的良好指标。(c)2007年爱思唯尔公司All rights reserved.
Background: O-6-Methylguanine-DNA rnethyltransferase is a DNA repair protein. Epigenetic silencing of MGMT function by its promoter hypermethylation is considered to contribute to carcinogenesis. If loss of function in MGMT is related to tumor progression, the immunohistochemical method may predict the malignant change of gliomas.Method: We investigated the expression of MGMT by immunohistochemical method in 28 supratentorial hemispheric diffuse astrocytomas. The prognostic significance of MGMT expression, proliferation index (MIB-1), and various clinical factors was evaluated.Results: There were 19 MGMT-positive and 9 MGMT-negative astrocytomas. Their rates of malignant transformation at 5 years were 12.3% and 51.4%, respectively. The difference was significant in the univariate (P = .004) and multivariate analyses (P = .044). Age, sex, extent of surgery, MIB-1 value, and radiation therapy at initial treatment did not correlate with the malignant progression. The 10-year overall Survival rates were 71.8% and 58.3% in the patients with MGMT-positive and MGMT-negative tumors, respectively, and were not significantly different between these 2 groups (P = .079). Two long-term survivors with MGMT-negative tumor responded well to nitrosourea-based chemotherapy and lived more than 8 years after malignant transformation. The patients' age (P = .0047) and the degree of surgical removal (P = .0082) affected the overall survival in the univariate analysis. In the multivariate analysis, none of these factors reached significance.Conclusion: Although the status of MGMT did not affect the overall survival, immunohistochemical evaluation of MGMT expression may be a good marker for tumor progression. (c) 2007 Elsevier Inc. All rights reserved.