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Title: [Prognostic implication of alterations in epidermal growth factor receptor and MGMT in glioblastoma].
Author: Zhang LY, Ge HJ, Wang LM, Zhao LH, Liu L, Zhang DJ, Cai YN, Lu DH, Piao YS.
Journal: Zhonghua Bing Li Xue Za Zhi; 2019 Mar 08; 48(3):186-191. PubMed ID: 30831643.
Abstract:
Objective: To investigate the prognostic impact of alterations of epidermal growth factor receptor(EGFR) and MGMT in glioblastoma. Methods: The retrospective study included 161 supratentorial glioblastomas diagnosed in the Department of Pathology, Xuanwu Hospital, Capital Medical University from 2009 to 2015. EGFR and EGFRvⅢ protein expression was detected by immunohistochemistry; EGFR amplification was detected by fluorescence in situ hybridization; MGMT promoter methylation was detected by pyrosequencing. The change of molecular genetics EGFR and MGMT and outcome were assessed statistically. Results: There were 161 patients, including 85 (52.8%) males and 76 (47.2%) females. The mean age was 53 years, and the median overall survival was 13 months. The integrated classification of glioblastoma included 16 IDH-mutant, 134 wild type, and 11 NOS. The rate of overexpression of EGFR protein was 32.9%(53/161), and that of EGFR amplification was 37.5%(18/48). There was high concordance between immunohistochemistry and FISH(85.4%, Kappa=0.475, P<0.01) and between the level of EGFR protein and EGFR amplification (P<0.01). Twelve cases showed EGFRvⅢ expression, and all also showed EGFR protein overexpression; 149 cases were EGFRv Ⅲ wild type, and EGFR protein overexpression was seen in 27.5%(41/149) of cases. There was no correlation between EGFR and EGFRv Ⅲ expression. Of all cases, 70.2%(106/151) showed MGMT promoter methylation by pyrosequencing. The changes of molecular genetics of EGFR and MGMT were not related. EGFR amplification and protein overexpression had no significant relationship with prognosis. Patients with EGFRv Ⅲ-mutant had shorter survival time than the EGFRv Ⅲ-wild type(P=0.014); patients with MGMT promoter methylation had better prognosis than without (PFS:P=0.002,OS:P=0.006),and MGMT promoter methylation was an independent predictor for overall survival (HR=0.269, 95%CI 0.124-0.583, P=0.001). Conclusions: EGFR protein expression by immunohistochemistry correlates with the status of EGFR amplification. Patients with EGFRv Ⅲ-mutant tumors have poorer prognosis than that with EGFRv Ⅲ-wild type tumors. MGMT promoter methylation is closely associated with prognosis and an independent predictor for overall survival. 目的： 探讨胶质母细胞瘤中表皮生长因子受体（EGFR）和MGMT的改变及其与预后的关系。 方法： 回顾性分析2009至2015年经首都医科大学宣武医院病理科诊断的161例幕上胶质母细胞瘤，运用全自动免疫组织化学染色检测表皮生长因子受体（EGFR）蛋白表达和EGFRvⅢ突变，荧光原位杂交（FISH）检测EGFR扩增；用焦磷酸测序法检测MGMT启动子甲基化情况。分析EGFR和MGMT的分子遗传学改变及其与预后的关系。 结果： 161例患者中，男性85例（52.8%），女性76例（47.2%）。患者平均年龄53岁，中位生存期13个月。胶质母细胞瘤整合分型为IDH突变型16例，IDH野生型134例，非特指型11例。EGFR蛋白高表达率为32.9%（53/161），EGFR扩增阳性率为37.5%（18/48），两者一致率高达85.4%（Kappa=0.475，P<0.01），EGFR蛋白表达水平与EGFR扩增情况之间存在显著相关性（P<0.01）。免疫组织化学检测到EGFRvⅢ突变型病例中12/12存在EGFR蛋白高表达，EGFRvⅢ野生型病例中27.5%（41/149）EGFR蛋白高表达，两者无相关性。70.2%（106/151）的病例MGMT启动子甲基化，EGFR和MGMT的分子遗传学改变无相关性。生存分析结果：EGFR扩增情况、EGFR蛋白表达水平与预后无关；EGFRvⅢ突变型患者的无进展生存期短于野生型患者（P=0.014）。MGMT启动子甲基化病例比未甲基化病例的预后好（无进展生存期P=0.002，总生存期P=0.006），MGMT启动子甲基化是总生存期的独立预后因素（HR=0.269，95% CI：0.124~0.583，P=0.001）。 结论： 在胶质母细胞瘤应用免疫组织化学检测EGFR蛋白表达水平可以反映EGFR基因扩增情况，EGFRvⅢ突变型患者比野生型的预后差，MGMT启动子甲基化与预后有关，是独立的预后因素。.

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