Background: It has been proven that epidermal growth factor receptor (EGFR) mutation is the most important predictive factor for determining the effect of EGFR tyrosine kinase inhibitors (TKIs) applied to non-small cell lung cancer (NSCLC) patients. The patients with EGFR mutations response better to TKIs. To detect EGFR mutation has been particularly essential to select first-line treatment for lung cancer patients. To research and analyze the sensitivity and specificity of immunohistochemistry (IHC) using mutation specific antibodies in detecting EGFR mutations compared with DNA sequencing, and further evaluate the accuracy and clinical application value of IHC.
Methods: All required articles in Pubmed database were searched. The deadline of retrieval was March 26, 2013. Then further screening the articles based on the inclusion and exclusion criteria. Meta analysis of diagnostic test was applied to analyze the sensitivity and specificity of IHC compared with DNA sequencing for the detection of EGFR mutations.
Results: Ten articles were included in the meta analysis, there were 1,679 samples in L858R group and 1,041 samples in E746-A750del group. The DOR were 225.17 (95%CI: 55.67-910.69) and 267.16 (95%CI: 132.45-538.88) respectively; the AUC of SROC were 0.948,4 (SEAUC=0.014,4) and 0.981,3 (SEAUC=0.009,9) respectively; the Q values were 0.888,3 (SEQ*=0.019,2) and 0.939,7 (SEQ*=0.019,1) respectively.
Conclusions: The specificity and sensitivity of IHC method using these two mutation-specific antibodies were relatively high. As a screening method for EGFR mutations, the IHC with mutation specific antibodies is of clinical value.
背景与目的 已有的研究表明：表皮生长因子受体（epidermal growth factor receptor, EGFR）基因突变是非小细胞肺癌（non-small cell lung cancer, NSCLC）患者应用表皮生长因子受体酪氨酸激酶抑制剂（EGFR tyrosine kinase inhibitor, EGFR-TKI）治疗疗效的最重要的预测因子。EGFR基因突变的患者对于使用TKIs分子靶向药物治疗疗效更敏感。其突变检测对肺癌一线靶向治疗选择尤为关键。研究分析特异性抗体免疫组化法（immunohistochemistry, IHC）检测EGFR突变与DNA测序法比较的敏感度与特异度，明确该方法准确性及临床应用价值。 方法 通过Pubmed数据库检索所有符合检索条件的文献，末次检索日期2013年3月26日，根据纳入和排除标准进行进一步筛选，采用诊断试验meta分析方法，分析特异性抗体免疫组化方法与DNA直接测序法对比的敏感度与特异度。结果 10篇文献纳入meta分析，L858R 1,679例，E746-A750del 1,041例，诊断比值比（diagnositic odds ratio, DOR）分别为225.17（95%CI: 55.67-910.69）和267.16（95%CI: 132.45-538.88）；SROC曲线AUC分别为0.948,4（SEAUC=0.014,4）和0.981,3（SEAUC=0.009,9），Q*统计量分别为0.888,3（SEQ*=0.019,2）和0.9397（SEQ*=0.019,1）。结论 以上两种特异性抗体IHC鉴别EGFR突变的特异度高，灵敏度较高，作为筛查突变方法可行性高，具有一定的临床应用价值。