Objectives: To evaluate the sensitivity and specificity of immunohistochemistry (IHC) for detecting common epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) and to estimate the cost-effectiveness of IHC testing.
Methods: A total of 208 NSCLC patients were included in the trial, and the EGFR mutation status in the patients were detected by PCR and IHC. Two mutation-specific antibodies against the most common exon 19 deletion (clone SP111) and exon 21 L858R mutation (clone SP125) were tested by using automated immunostainer. A cost-effectiveness analysis model was built for the analysis of optimal detection scheme.
Results: With a cutoff value of IHC 1+, the overall sensitivity and specificity of the IHC-based method compared with the PCR-based method were 81.7% (95% CI 72.4% to 89.0%) and 94.7% (95% CI 92.6% to 99.5%), respectively. EGFR 19del mutation was detected by SP111 antibody with a sensitivity of 65.9% (95% CI 49.4% to 79.9%) and specificity of 98.8% (95% CI 95.7% to 99.9%). EGFR L858R mutation was detected by SP125 antibody with a sensitivity of 94.2% (95% CI 84.1% to 98.8%) and specificity of 99.4% (95% CI 96.5% to 100%). The IHC and PCR cost ratio needed to be 1-to-3 or more in our patients to economically justify before the use of IHC.
Conclusions: The study confirms an excellent specificity with fairly good sensitivity of IHC and mutation-specific antibodies for common EGFR mutations. It is cost-effective to use IHC method to detect EGFR mutation first when the IHC and PCR cost ratio is 1-to-3 or more in Chinese populations.
目的: 采用免疫组织化学(immunohistochemistry，IHC)检测非小细胞肺癌(non-small cell lung cancer，NSCLC)常见的表皮生长因子受体(epidermal growth factor receptor，EGFR)突变，并对IHC检测的敏感性、特异性和成本-效益进行评估。方法: 应用PCR和IHC检测208例NSCLC患者的EGFR突变情况。用全自动免疫染色仪检测两种针对最常见突变的特异性抗体，即EGFR外显子19的缺失突变(19del突变)抗体(克隆号SP111)和外显子21的L858R突变抗体(克隆号SP125)。同时构建成本-效益模型进行最优检测方案分析。结果: 以IHC 1+为阳性阈值，与PCR检测相比较，IHC检测的总体敏感性和特异性分别为81.7%(95% CI：72.4%~89.0%)和94.7%(95% CI：92.6%~99.5%)；SP111抗体检测EGFR 19del突变的敏感性为65.9%(95% CI：49.4%~79.9%)，特异性为98.8%(95% CI：95.7%~99.9%)；SP125抗体检测EGFR L858R突变的敏感性为94.2%(95% CI：84.1%~98.8%)，特异性为99.4%(95% CI：96.5%~100%)。在本研究的患者群体中，当IHC和PCR的成本比达到1꞉3或差距更大时，优先使用IHC检测EGFR突变是合理的。结论: IHC检测NSCLC常见的EGFR突变具有良好的特异性和较好的敏感性。在中国人群中，当IHC和PCR的成本比为1꞉3或差距更大时，优先采用IHC方法检测EGFR突变是经济有效的。.
Keywords: epidermal growth factor receptor; immunohistochemistry; lung cancer; sensitivity; specificity.