表皮生长因子受体2在老年颅内脑膜瘤中的表达及预后意义  

Expression and prognostic significance of epidermal growth factor receptor 2 in elderly intracranial meningioma

作　　者：孙若水 惠培刚 肖哲 Sun Ruoshui;Hui Peigang;Xiao Zhe(Department of Neurosurgery,Qingyang People's Hospital,Qingyang 745000,Gansu Province,China)

机构地区：[1]庆阳市人民医院神经外科,7450000

出　　处：《中华老年心脑血管病杂志》2024年第9期1059-1064,共6页Chinese Journal of Geriatric Heart,Brain and Vessel Diseases

基　　金：甘肃省科技计划项目(22JR5RM1004)。

摘　　要：目的 探讨人表皮生长因子受体2(human epidermalgrowth factor receptor-2,HER2)在老年颅内脑膜瘤中的表达及预后意义。方法 连续选取2021年2月至2023年1月于庆阳市人民医院神经外科行手术切除的老年颅内脑膜瘤患者52例。根据世界卫生组织(World Health Organization, WHO)分级分为WHOⅠ级组40例,WHOⅡ/Ⅲ级组12例;根据磷酸化HER2(pHER2)分为pHER2低表达组39例和pHER2高表达组13例。采用免疫组织化学法检测HER2的胞外结构域(ectodomain, ECD)、胞内结构域(intracellular Domain, ICD)和磷酸化受体(6B12)的表达,采用双探针荧光原位杂交法检测脑膜瘤患者HER2基因扩增,术后随访并记录复发生存时间和总生存时间,采用Cox比例风险回归模型和Kaplan-Meier生存曲线分析HER2表达与老年脑膜瘤患者复发和死亡风险的关系。结果 老年脑膜瘤患者ICD-CB11和ICD-3B5阳性率均为100.00%,而ECD-SP3和6B12(pHER2)的阳性率分别为61.54%(32/52)和25.00%(13/52)。在正常脑膜组织中,4种抗体免疫反应均为阴性。此外,WHOⅠ级组与WHOⅡ/Ⅲ级组HER2表达比较无显著差异(P>0.05)。所有老年脑膜瘤患者均未检测到HER2基因扩增,HER2信号总数和CEP17信号总数的比值为0.84~1.35(1.09±0.11)。经单因素和多因素Cox比例风险回归分析,结果显示,pHER2高表达是老年脑膜瘤患者复发和死亡风险的独立危险因素(P<0.05)。随访期间,与pHER2高表达组比较,pHER2低表达组无复发生存率高、中位无复发生存时间长,差异有统计学意义(74.36%vs 30.77%,1.66年vs 0.56年,P_(log rank)<0.01)。在生存分析中,与pHER2高表达组比较,pHER2低表达组总生存率高,中位总生存时间长,差异有统计学意义(82.05%vs 46.15%,2.27年vs 0.58年,P_(log rank)<0.01)。结论 HER2在老年颅内脑膜瘤患者组织中呈过表达,且pHER2过表达与颅内脑膜瘤患者复发和死亡风险增加相关。HER2可能作为老年脑膜瘤患者的预后预测工具,并有望成为脑Objective To investigate the expression and prognostic significance of human epidermal growth factor receptor 2(EGFR 2,also called HER2 or c-ErbB2) in elderly intracranial meningiomas.Methods A total of 52 elderly patients with intracranial meningioma who underwent surgical resection in our department from February 2021 to January 2023 were consecutively recruited in this study.According to the World Health Organization(WHO) classification, 40 cases were assigned into WHO grade Ⅰ and 12 cases into WHO grade Ⅱ/Ⅲ.Based on the phosphorylation level of HER2(p-HER2),there were 39 cases with low p-HER2 expression and 13 cases with high expression.The expression of HER2 extracellular domain(ECD),intracellular domain(ICD) and phosphorylated receptor(6B12) were detected by immunohistochemistry.Double probe fluorescence in situ hybridization(FISH) was used to detect the amplification of HER2.Time to recurrence(TTR) and overall survival(OS) were recorded during follow-up.Cox proportional hazards regression model and Kaplan-Meier survival curve were employed to analyze the relationship of HER2 expression and recurrence and death risk in these patients.Results The positive rate of ICD-CB11 and ICD-3B5 was both 100%,while that of ECD-SP3 and 6B12(p-HER2) was 61.54%(32/52) and 25.00%(13/52),respectively in the elderly patients.In normal meningeal tissues, negative results were observed in all above four antibody immune responses.In addition, there was no significant difference in HER2 expression between WHO group Ⅰ and WHO group Ⅱ/Ⅲ(P>0.05).HER2 gene amplification was not detected in all elderly patients with meningioma, and the ratio of HER2 to CEP17 signals was 1.09±0.11,ranging from 0.84 to 1.35.Univariate and multivariate COX proportional hazard regression analysis showed that high expression of p-HER2 was an independent risk factor for recurrence and death in elderly patients with meningioma(P<0.05).During follow-up, the patients with low p-HER2 expression had higher relapse-free survival rate and longer media

关 键 词：脑膜瘤 预后 预测 表皮生长因子受体2 

分 类 号：R739.45[医药卫生—肿瘤]