突变特异性抗体检测肺腺癌EGFR基因突变的临床应用  

The clinical application of mutation specific antibodies to detect EGFR mutation in lung adenocarcinoma

作　　者：董丹丹[1] 徐钢[1] 李芳华[1] 胥颖[1] 李科[1] 黄娟[2] 

机构地区：[1]四川省医学科学院.四川省人民医院病理科,四川成都610072 [2]泸州医学院病理学教研室,四川泸州646000

出　　处：《实用医院临床杂志》2014年第4期71-75,共5页Practical Journal of Clinical Medicine

基　　金：四川省卫生厅科研基金资助项目(编号:130275);泸州市科技局项目资助(编号:2013-S-47)

摘　　要：目的评估两种表皮生长因子受体(epithelial growth factor receptor,EGFR)基因突变特异性抗体在肺腺癌石蜡组织样本中的检测价值。方法收集临床肺腺癌石蜡组织标本76例,采用L858R突变和19外显子E746-A750缺失特异性抗体进行免疫组织化学标记,同时提取DNA用ARMS法进行EGFR突变分析。结果 76例石蜡组织样本中,ARMS法检测出L858R突变14例,19外显子缺失14例,L861Q突变1例,野生型47例。免疫组织化学法检测L858R突变和19外显子E746-A750缺失敏感性均为79%,特异性分别为92%、79%。阴性预测值分别达到95%、94%。若将阳性阈值定为2+,L858R突变抗体均无假阳性病例(8/8),19外显子E746-A750缺失抗体出现1例假阳性病例(7/8),检出阳性病例特异性达94%(15/16)。结论采用EGFR突变特异性抗体免疫标记石蜡组织样本,可作为临床筛查突变阴性病例的有效手段。Objective To evaluate the clinical values of two EGFR mutant-specific antibodies in effusion immunohistochemistry to detect the relevant EGFR mutations in NSCLC.Methods Immunohistochemistry using two antibodies binding specifically to the major forms of mutant EGFR,L858 R and E746-A750 deletion,was performed on formalin fixed paraffin-embedded（FFPE） tissue samples obtained from 76 patients with lung adenocarcinoma.At the same time,DNA in the FFPE tissue samples was extracted and EGFRmutation was analyzed by using Amplification Refractory Mutation System（ARMS）.Results Of the 76 FFPE tissue samples,ARMS identified L858 R mutation in 14 cases,deletions in exon 19 in 14 cases,L861 Q mutation in 1 case,and wild-type EGFR in 47 cases.Effusion immunohistochemistry with these two mutant-specific antibodies exhibited a sensitivity of 79% and 79%,a specificity of 92%and 79% and a negative protective value of 95% and 94% in identifying predefined L858 R and delE746-A750 mutations,respectively.When the cutoff value of 2＋ was used as positive by IHC,no wild type case was found by using L858 R mutant-specific antibodies（8/8）,and only one wild type case was identified by using delE746-A750 mutant-specific antibodies（7/8）.The specificity was 94%（15/16） and 79%,respectively.Conclusion Immunohistochemistry could be introduced into clinical practice to identify EGRF negative L858 R and delE746-A750 mutations in NSCLC patients.

关 键 词：肺腺癌 表皮生长因子受体 基因 突变 免疫组织化学 

分 类 号：R734.2[医药卫生—肿瘤]