肺腺癌表皮生长因子受体基因突变特异性抗体的应用

Mutation-specific antibodies for detection of epidermal growth factor receptor mutations in patients with lung adenocarcinoma

目的验证针对表皮生长因子受体（EGFR）基因经典突变——19de1E746．A750／211858R的特异性抗体敏感度和特异度，从而探讨应用免疫组织化学检测EGFR基因突变的临床意义。方法应用免疫组织化学方法（EnVision二步法）、Q评分体系及ROC曲线检测309例肺腺癌标准EGFR基因突变状态，并与聚合酶链反应（PCR）-DNA测序结果做比较，评价de1EGFR和L858R两种特异性抗体检测EGFR基因突变状态的诊断价值。结果经过PCR—DNA直接测序的肺腺癌标本中，92例为外显子19de1E746-A750突变，110例为外显子21L858R点突变。用delEGFR抗体检测外显子19de1E746-A750突变的敏感度为84．8％（78／92），特异度为77．6％（83／107），ROC曲线下面积为0．885，最佳分界值为85．00；用L858R抗体检测外显子21L858R点突变的敏感度为94．5％（104／110），特异度为62．5％（55／88），ROC曲线下面积为0．924，最佳分界值为97．50。结论delEGFR和L858R两种EGFR突变特异性抗体可用于检测EGFR基因的突变状态，并且结果判读使用Q评分及ROC曲线评价检测结果有较好的临床应用价值。

Objective To examine the sensitivity and specificity of the two epidermal growth factor receptor hotspot mutation antibodies-delE746-A750 and L858R in lung adenocarcinoma, and to discuss the value of the two antibodies for detecting these two ＂classic mutations＂ by immunohistochemistry. Methods With Q-scoring assessment and ROC curve analysis, immunohistochemistry was used to screen a panel of 309 paraffin-embedded non-small cell lung cancer （NSCLC） tumor samples, of which EGFR gene mutational status was previously documented by PCR-DNA sequencing. Results Three hundred and nine NSCLC tumor samples conclude 92 NSCLC cases with 19delE746-A750 and 110 with 21L858R. Using DelEGFR antibody to detect 19delE746-A750 demonstrated sensitivity and specificity of 84. 8% （78/92） and 77. 6% （83/107）, respectively. Choosing the best cut-off value of 85.00, it achieved the maximum area under the curve （AUC： 0. 885 ）. L858R antibody to detect 21L858R showed sensitivity and specificity of 94. 5% （104/110） and 62.5% （55/88）, respectively. Choosing the best cut-off value of 97.50, it achieved the maximum area under the curve （ AUC ： 0. 924）. Conclusion By using Q-scoring assessment and ROC curve analysis, the two antibodies （delEGFR and L858R） can been used to identify EGFR gene mutations present in lung adenocarcinomas.