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

• Published in: Clinical cancer research Vol. 17; no. 24; pp. 7796 - 7807
• Main Authors: MASCAUX, Celine, WYNES, Murry W, NAGAO, Toshitaka, YOSHIDA, Koichi, OHIRA, Tatuso, IKEDA, Norihiko, HIRSCH, Fred R, KATO, Yasufumi, TRAN, Cindy, ASUNCION, Bernadette Reyna, ZHAO, Jason M, GUSTAVSON, Mark, RANGER-MOORE, Jim, GAIRE, Fabien, MATSUBAYASHI, Jun
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 15.12.2011
• Subjects: Adult; Aged; Aged, 80 and over; Antibodies; Antineoplastic agents; Binding Sites; Biological and medical sciences; Cancer; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - metabolism; Data processing; Epidermal growth factor receptors; Female; Fluorescent Antibody Technique - methods; Gefitinib; Humans; Image Processing, Computer-Assisted - methods; Immunohistochemistry; Immunohistochemistry - methods; Kaplan-Meier Estimate; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; Male; Medical sciences; Middle Aged; Multivariate Analysis; Mutation; Non-small cell lung carcinoma; Outcome Assessment (Health Care) - statistics & numerical data; Pharmacology. Drug treatments; Pneumology; Prognosis; Proportional Hazards Models; Protein Kinase Inhibitors - therapeutic use; Protein-tyrosine kinase; Quinazolines - therapeutic use; Receptor, Epidermal Growth Factor - antagonists & inhibitors; Receptor, Epidermal Growth Factor - biosynthesis; Receptor, Epidermal Growth Factor - genetics; Survival; Therapeutic applications; Tissue Array Analysis; Tumors of the respiratory system and mediastinum; Immunohistochemistry; Lung disease; Respiratory disease; Antibody; Lung cancer; Malignant tumor; non-small cell lung carcinoma; Gene expression; EGFR tyrosine kinase inhibitor; Protein; Epidermal growth factor receptor; Anatomic pathology; Technology; Bronchus disease; Predictive factor; Cancer
• ISSN: 1078-0432; 1557-3265; 1078-0432
• DOI: 10.1158/1078-0432.ccr-11-0209

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.