title: 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.
abstract: BACKGROUND
  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). EGFR ID (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. ©2011 AACR.
authors: Divisions of Medical Oncology and Pathology, University of Colorado Denver, Aurora, Colorado, USA.
authors: Celine
authors: C
authors: Mascaux
authors: Murry W
authors: MW
authors: Wynes
authors: Yasufumi
authors: Y
authors: Kato
authors: Cindy
authors: C
authors: Tran
authors: Bernadette Reyna
authors: BR
authors: Asuncion
authors: Jason M
authors: JM
authors: Zhao
authors: Mark
authors: M
authors: Gustavson
authors: Jim
authors: J
authors: Ranger-Moore
authors: Fabien
authors: F
authors: Gaire
authors: Jun
authors: J
authors: Matsubayashi
authors: Toshitaka
authors: T
authors: Nagao
authors: Koichi
authors: K
authors: Yoshida
authors: Tatuso
authors: T
authors: Ohira
authors: Norihiko
authors: N
authors: Ikeda
authors: Fred R
authors: FR
authors: Hirsch
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001665:Binding Sites; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D005455:Fluorescent Antibody Technique / Q000379:methods; D000077156:Gefitinib; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D007150:Immunohistochemistry / Q000379:methods; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D017063:Outcome Assessment, Health Care / Q000706:statistics & numerical data; D011379:Prognosis; D016016:Proportional Hazards Models; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011799:Quinazolines / Q000627:therapeutic use; D046888:Tissue Array Analysis
chemical_list: D047428:Protein Kinase Inhibitors; D011799:Quinazolines; C512478:EGFR protein, human; D066246:ErbB Receptors; D000077156:Gefitinib