Divisions of Medical Oncology and Pathology, University of Colorado Denver, Aurora, Colorado, USA.
Clin Cancer Res. 2011 Dec 15;17(24):7796-807. doi: 10.1158/1078-0432.CCR-11-0209. Epub 2011 Oct 12.
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).
Specimens from 98 gefitinib-treated NSCLC Japanese patients were evaluated by IHC (n = 98 of 98) and AQUA technology (n = 70 of 98). EGFR ID (5B7)- and ED-specific antibodies (3C6 and 31G7) were compared.
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.
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. ©2011 AACR.
由于结果存在冲突，表皮生长因子受体（EGFR）蛋白在非小细胞肺癌（NSCLC）中的表达不建议用于预测对 EGFR 酪氨酸激酶抑制剂（TKI）的反应，所有这些结果均使用检测 EGFR 外显子（ED）的抗体。我们使用检测细胞内结构域（ID）的抗体检测 EGFR 蛋白表达对 EGFR TKI 反应的预测价值，并比较荧光自动化定量分析（AQUA）技术与免疫组织化学（IHC）。
对 98 例接受吉非替尼治疗的日本 NSCLC 患者的标本进行 IHC（98 例中的 98 例）和 AQUA 技术（98 例中的 70 例）评估。比较了 EGFR ID（5B7）和 ED 特异性抗体（3C6 和 31G7）。
使用 5B7 评估的 EGFR 表达在吉非替尼的应答者和无应答者中均明显高于 IHC 和 AQUA。ED 特异性抗体不能显著预测反应。使用 AQUA 和 ID 特异性抗体可获得最佳的预测性能，阳性预测值（PPV）/阴性预测值（NPV）分别为 50%和 87%。ID 特异性抗体和 AQUA 也可预测 EGFR 突变患者的应答者。ID 抗体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，对数秩，P=0.034）和总生存期（OS；38.6 个月 vs. 14.9 个月，P=0.040）延长相关。
使用 ID 特异性抗体的 EGFR 蛋白表达可特异性预测 NSCLC 患者对吉非替尼的反应，包括 EGFR 突变患者，并延长吉非替尼的 PFS/OS。这些数据表明，诊断抗体和方法的选择对于预测特定治疗的反应和结果很重要。潜在的临床应用需要进一步验证。临床癌症研究；17（24）；7796-807。©2011AACR。
