Department of Pathology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA.
J Mol Diagn. 2010 Mar;12(2):169-76. doi: 10.2353/jmoldx.2010.090140. Epub 2010 Jan 21.
EGFR mutations are the best predictors of response to EGFR kinase inhibitors in lung adenocarcinoma. We evaluated two mutation-specific monoclonal antibodies for the detection of EGFR mutations by immunohistochemistry (IHC), generated respectively against the L858R mutant and the exon 19 mutant with the common 15bp/5AA deletion. These two mutations account for approximately 90% of all EGFR mutations. IHC staining performed on 218 paraffin-embedded lung adenocarcinomas was assessed on a 0 to 3+ scale, and positivity cutoffs of 1+ and 2+ were compared. All cases were studied by standard molecular methods for these two mutations, and selected cases were also studied using higher sensitivity molecular assays. The EGFR L858R mutant antibody showed a sensitivity of 95% and a positive predictive value (PPV) of 99% with a positivity cutoff of 1+ and a sensitivity of 76% and a PPV of 100% with a positivity cutoff of 2+. The EGFR exon 19 mutant-specific antibody showed reduced sensitivity for exon 19 deletions other than 15bp. A positivity cutoff of 1+ resulted in a sensitivity of 85% and a PPV of 99%, whereas a 2+ cutoff gave a sensitivity of 67% and a PPV of 100%. IHC with EGFR mutant-specific antibodies could be used as a screen to identify most candidates for EGFR inhibitors.
表皮生长因子受体（EGFR）突变是预测肺腺癌对 EGFR 激酶抑制剂反应的最佳指标。我们评估了两种针对 EGFR 突变的突变特异性单克隆抗体，通过免疫组织化学（IHC）检测 EGFR 突变，分别针对 L858R 突变和外显子 19 突变（带有常见的 15bp/5AA 缺失）产生。这两种突变约占所有 EGFR 突变的 90%。对 218 例石蜡包埋的肺腺癌进行了 0 至 3+级的 IHC 染色评估，并比较了 1+和 2+的阳性截断值。所有病例均采用标准分子方法对这两种突变进行研究，选择的病例还采用更高灵敏度的分子检测方法进行研究。EGFR L858R 突变抗体的阳性截断值为 1+时，敏感性为 95%，阳性预测值（PPV）为 99%，敏感性为 76%，PPV 为 100%，阳性截断值为 2+。针对 EGFR 外显子 19 突变的特异性抗体对 15bp 以外的外显子 19 缺失的敏感性降低。阳性截断值为 1+时，敏感性为 85%，PPV 为 99%，而 2+截断值的敏感性为 67%，PPV 为 100%。针对 EGFR 突变的特异性抗体的 IHC 可作为筛选工具，以确定大多数 EGFR 抑制剂候选者。
