Overexpression of mutant EGFR protein indicates a better survival benefit from EGFR-TKI therapy in non-small cell lung cancer.
Overexpression of mutant EGFR protein indicates a better survival benefit from EGFR-TKI therapy in non-small cell lung cancer.
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DOI：
10.18632/oncotarget.10594
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发表时间：
2016-08-16
期刊：
影响因子：
--
通讯作者：
Lin D
中科院分区：
文献类型：
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作者：
Ling Y;Yang X;Li W;Li Z;Yang L;Qiu T;Guo L;Dong L;Li L;Ying J;Lin D
表皮生长因子受体（EGFR）是治疗非小细胞肺癌（NSCLC）的一个新靶点。EGFR突变肿瘤对EGFR酪氨酸激酶抑制剂（TKI）的反应良好。我们旨在确定免疫组织化学（IHC）检测NSCLC患者中EGFR L 858 R和del E746-A750突变的鉴别能力，并预测EGFR TKI反应。我们收集了200例NSCLC患者的标本，其EGFR突变状态已通过直接DNA测序验证。所有样本均采用EGFR突变特异性抗体进行IHC分析。染色后评分，计算敏感性、特异性、阳性预测值（PPV）和阴性预测值（NPV）。使用EGFR del E746-A750和L 858 R突变抗体的IHC的灵敏度、特异性、PPV和NPV分别为95.0%/95.1%、85.7%/94.1%、74.0%/91.8%和97.6%/96.5%。以评分2+和3+为阳性时，敏感性、特异性、PPV和NPV分别为53.3%/36.6%、99.3%/100%、97.0%/100%和83.2%/65.3%。突变型EGFR表达评分高的患者开始吉非替尼治疗后的中位无进展生存期（PFS）显著长于评分低的患者（31.0个月vs 13.0个月，p <0.05）。EGFR突变特异性抗体的IHC是检测NSCLC患者EGFR突变的一种有前景的筛查方法。此外，突变型EGFR表达的定量分析也可能预测TKI治疗携带敏感EGFR突变的NSCLC患者的疗效。
Epidermal growth factor receptor (EGFR) is a novel target for therapy in a subset of non-small cell lung cancer (NSCLC). Tumors with EGFR mutations showed good response to EGFR tyrosine kinase inhibitors (TKIs). We aimed to identify the discriminating capacity of immunohistochemistry (IHC) to detect EGFR L858R and del E746-A750 mutations in NSCLC patients and predict EGFR TKIs response. We collected specimens from 200 patients with NSCLC whose EGFR mutation status had been validated by direct DNA sequencing. IHC analyses using EGFR mutation-specific antibodies were employed for all samples. After staining and scoring, the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated. The sensitivity, specificity, PPV, and NPV of IHC using EGFR del E746-A750 and L858R mutation antibodies were 95.0%/95.1%, 85.7%/94.1%, 74.0%/91.8%, and 97.6%/96.5%, respectively. When score 2+ and 3+ were considered as positive, the sensitivity, specificity, PPV, and NPV were 53.3%/36.6%, 99.3%/100%, 97.0%/100%, and 83.2%/65.3%, respectively. The median progression-free survival (PFS) after the start of gefitinib treatment was significantly longer in patients with a high score for mutant EGFR expression than in those with a low score (31.0 versus 13.0 months, p <0.05). IHC with EGFR mutation-specific antibodies is a promising screening method for detecting EGFR mutations in NSCLC patients. Otherwise, quantitative analysis of mutant EGFR expression might also predict the efficacy of TKIs treatment for NSCLC patients harboring sensitive EGFR mutation.