title: Overexpression of mutant EGFR protein indicates a better survival benefit from EGFR-TKI therapy in non-small cell lung cancer.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pathology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Ling
authors.affiliation: Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Pathology, Peking University Cancer Hospital & Institute, Beijing, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Pathology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Wenbin
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Pathology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Pathology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Pathology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Tian
authors.initials: T
authors.lastname: Qiu
authors.affiliation: Department of Pathology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Guo
authors.affiliation: Department of Pathology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Dong
authors.affiliation: Department of Pathology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Pathology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Jianming
authors.initials: J
authors.lastname: Ying
authors.affiliation: Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Pathology, Peking University Cancer Hospital & Institute, Beijing, China.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Lin
mesh_terms: D000328:Adult; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D005260:Female; D000077156:Gefitinib; D006801:Humans; D007150:Immunohistochemistry; 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 / Q000379:methods; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011799:Quinazolines / Q000627:therapeutic use*
chemical_list: D047428:Protein Kinase Inhibitors; D011799:Quinazolines; C512478:EGFR protein, human; D066246:ErbB Receptors; D000077156:Gefitinib
keywords: activating EGFR mutation; immunohistochemistry; mutation-specific antibodies; non-small cell lung cancer; survival