EGFR Protein Expression in Non-Small Cell Lung Cancer Predicts Response to an EGFR Tyrosine Kinase Inhibitor-A Novel Antibody for Immunohistochemistry or AQUA Technology
EGFR Protein Expression in Non-Small Cell Lung Cancer Predicts Response to an EGFR Tyrosine Kinase Inhibitor-A Novel Antibody for Immunohistochemistry or AQUA Technology
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DOI：
10.1158/1078-0432.ccr-11-0209
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发表时间：
2011-12-15
影响因子：
11.5
通讯作者：
Hirsch, Fred R.
中科院分区：
文献类型：
--
作者：
Mascaux, Celine;Wynes, Murry W.;Hirsch, Fred R.
前言：非小细胞肺癌(NSCLC)中表皮生长因子受体(EGFR)蛋白的表达不被推荐用来预测EGFR酪氨酸激酶抑制剂(TKI)的疗效，因为所有的结果都是用检测EGFR外区(ED)的抗体来预测的。我们用一种检测细胞内结构域(ID)的抗体来检测EGFR TKI对EGFR TKI反应的预测价值，并将基于荧光的自动定量分析(AquA)技术与免疫组织化学(IHC)技术进行比较。方法：对98例接受吉非替尼治疗的日本NSCLC患者的标本进行IHC(n=98)和Aqua技术(n=70)评估。结果：Gefitinib对5B7有反应者的EGFR表达显著高于无应答者(P<0.05)。ED特异性抗体并不能显著预测疗效。使用水和ID特异性抗体对应答者的预测效果最好，阳性预测值和阴性预测值(PPV/NPV)分别为50%和87%。具有ID特异性抗体和AQA的EGFR表达也可以预测EGFR突变患者的应答。使用ID抗体的EGFR表达增加与吉非替尼治疗的中位无进展生存期(PFS；11.7个月vs.5.0，对数等级，P=0.034)和总生存期(OS；38.6vs.14.9，P=0.040)相关。结论：使用ID特异性抗体表达EGFR蛋白可以特异性地预测非小细胞肺癌患者，包括EGFR突变患者，以及Gefitinib增加的PFS/OS。这些数据表明，诊断抗体和方法学的选择对预测特定治疗的反应和结果很重要。其潜在的临床应用有待进一步验证。临床癌症研究中心；17(24)；7796-807。(C)2011年AACR。
Introduction: Epidermal growth factor receptor (EGFR) protein expression in non-small cell lung cancer (NSCLC) is not recommended for predicting response to EGFR tyrosine kinase inhibitors (TKI) due to conflicting results, all using antibodies detecting EGFR external domain (ED). We tested the predictive value of EGFR protein expression for response to an EGFR TKI with an antibody that detects the intracellular domain (ID) and compared fluorescence-based Automated QUantitative Analysis (AQUA) technology to immunohistochemistry (IHC).Methods: Specimens from 98 gefitinib-treated NSCLC Japanese patients were evaluated by IHC (n = 98 of 98) and AQUA technology (n = 70 of 98). EGFRID(5B7)- and ED-specific antibodies (3C6 and 31G7) were compared.Results: EGFR expression evaluated with 5B7 was significantly higher in responders versus nonresponders to gefitinib both with IHC and with AQUA. ED-specific antibodies did not significantly predict response. Using AQUA and ID-specific antibody resulted in the best prediction performance with a positive and negative predictive value (PPV/NPV) for responders of 50% and 87%, respectively. EGFR expression with ID-specific antibody and AQUA also predicted responders in EGFR-mutated patients. Increased EGFR expression with the ID antibody is associated with increased median progression free survival (PFS; 11.7 months vs. 5.0, log rank, P = 0.034) and overall survival (OS; 38.6 vs. 14.9, P = 0.040) from gefitinib therapy.Conclusions: EGFR protein expression using an ID-specific antibody specifically predicts response to gefitinib in NSCLC patients, including in EGFR-mutated patients, and increased PFS/OS from gefitinib. These data suggest that the choice of diagnostic antibody and methodology matters to predict response and outcome to specific therapies. The potential clinical application needs further validation. Clin Cancer Res; 17(24); 7796-807. (C) 2011 AACR.