Hitij Nina Turnšek, Kern Izidor, Sadikov Aleksander, Knez Lea, Stanič Karmen, Zwitter Matjaž, Cufer Tanja
University Clinic Golnik, Golnik, Slovenia.
University Clinic Golnik, Golnik, Slovenia.
Clin Lung Cancer. 2017 May;18(3):e187-e196. doi: 10.1016/j.cllc.2016.11.021. Epub 2016 Dec 2.
The sensitivity and specificity of immunohistochemistry (IHC) was compared with the standard polymerase chain reaction (PCR)-based method for detecting common activating epidermal growth factor receptor (EGFR) mutations in non-small-cell lung cancer (NSCLC). Additionally, we evaluated predictive value of IHC EGFR mutation-positive status for EGFR tyrosine kinase inhibitor (TKI) treatment outcome and estimated cost-effectiveness for the upfront IHC testing.
The trial included 79 consecutive EGFR mutation-positive and 29 EGFR mutation-negative NSCLC cases diagnosed with reflex PCR-based testing. Two mutation-specific antibodies against the most common exon 19 deletion, namely E746-A750del (clone SP111) and L858R mutation (clone SP125) were tested by using automated immunostainer. Sixty of 79 EGFR mutation-positive cases were treated with EGFR TKIs for advanced disease and included in treatment outcome analysis. A decision tree was used for the cost-effectiveness analysis.
The overall sensitivity and specificity of the IHC-based method compared with the PCR-based method were 84.8% (95% confidence interval [CI] 74.6-91.6) and 100% (95% CI 85.4-100), respectively. The median progression-free survival (PFS) and overall survival (OS) of patients with IHC-positive EGFR mutation status were highly comparable to the total cohort (PFS: 14.3 vs. 14.0 months; OS: 34.4 vs. 34.4 months). The PCR and IHC cost ratio needs to be approximately 8-to-1 and 4-to-1 in White and Asian populations, respectively, to economically justify upfront use of IHC.
The trial confirmed an excellent specificity with fairly good sensitivity of IHC with mutation-specific antibodies for common EGFR mutations and the accuracy of IHC testing for predicting response to EGFR TKIs. The use of upfront IHC depends mainly on the population EGFR mutation positivity probability.
将免疫组织化学（IHC）的敏感性和特异性与基于标准聚合酶链反应（PCR）的方法进行比较，以检测非小细胞肺癌（NSCLC）中常见的激活型表皮生长因子受体（EGFR）突变。此外，我们评估了免疫组化EGFR突变阳性状态对EGFR酪氨酸激酶抑制剂（TKI）治疗结果的预测价值，并估计了前期免疫组化检测的成本效益。
该试验纳入了79例连续的经基于PCR的检测确诊为EGFR突变阳性和29例EGFR突变阴性的NSCLC病例。使用自动免疫染色仪检测两种针对最常见的19外显子缺失的突变特异性抗体，即E746-A750del（克隆号SP111）和L858R突变（克隆号SP125）。79例EGFR突变阳性病例中的60例因晚期疾病接受了EGFR TKIs治疗，并纳入治疗结果分析。使用决策树进行成本效益分析。
与基于PCR的方法相比，基于免疫组化的方法的总体敏感性和特异性分别为84.8%（95%置信区间[CI]74.6-91.6）和100%（95%CI 85.4-100）。免疫组化EGFR突变阳性状态患者的无进展生存期（PFS）和总生存期（OS）中位数与整个队列高度可比（PFS：14.3个月对14.0个月；OS：34.4个月对34.4个月）。在白人和亚洲人群中，PCR与免疫组化的成本比分别需要约为8比1和4比1，才能在经济上证明前期使用免疫组化是合理的。
该试验证实了免疫组化使用突变特异性抗体检测常见EGFR突变具有出色的特异性和相当好的敏感性，以及免疫组化检测预测EGFR TKIs反应的准确性。前期使用免疫组化主要取决于人群EGFR突变阳性概率。
