title: Concurrence of EGFR amplification and sensitizing mutations indicate a better survival benefit from EGFR-TKI therapy in lung adenocarcinoma patients.
abstract: OBJECTIVE
  Tumor heterogeneity, which causes different EGFR mutation abundance, is believed to be responsible for varied progression-free survival (PFS) in lung adenocarcinoma (ADC) patients receiving EGFR-TKI treatment. Frequent EGFR amplification and its common affection in EGFR mutant allele promote the hypothesis that EGFR mutant abundance might be determined by EGFR copy number variation and therefore examination of EGFR amplification status in EGFR mutant patients could predict the efficacy of EGFR-TKI treatment.
  
  
  METHODS
  In this study, 86 lung ADC patients, who harbored EGFR activating mutations and received EGFR-TKI treatment, were examined for EGFR amplification and expression by Dual-color Silver in situ Hybridization (DISH) and immunohistochemistry analysis, respectively.
  
  
  CONCLUSIONS
  Forty-one of 86 (47.7%) samples with EGFR activating mutations were identified with EGFR amplification. Patients with EGFR gene amplification had a significantly longer PFS than those without (16.3 vs. 9.1 months, p=0.004). The EGFR expression was then examined by immunohistochemistry analysis. Thirty-nine of 86 (45%) tumors had EGFR overexpression, which was significantly correlated with EGFR amplification (p=0.000). However, patients with EGFR overexpression exhibited no difference in PFS (14.1 vs. 13.3 months, p=0.797). In conclusion, EGFR amplification occurs frequently in lung ADC patients harboring EGFR activating mutations, and could serve as an indicator for better response from EGFR-TKI treatment.
authors.affiliation: Departments of Pathology, Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Shan
authors.affiliation: Departments of Medical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
authors.forename: Ziping
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Departments of Pathology, Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Guo
authors.affiliation: Departments of Medical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Sun
authors.affiliation: Departments of Pathology, Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
authors.forename: Tian
authors.initials: T
authors.lastname: Qiu
authors.affiliation: Departments of Pathology, Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Ling
authors.affiliation: Departments of Pathology, Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
authors.forename: Wenbin
authors.initials: W
authors.lastname: Li
authors.affiliation: Departments of Pathology, Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.affiliation: Departments of Pathology, Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
authors.forename: Xiuyun
authors.initials: X
authors.lastname: Liu
authors.affiliation: Departments of Pathology, Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Zheng
authors.affiliation: Departments of Pathology, Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China. Electronic address: nlu03@126.com.
authors.forename: Ning
authors.initials: N
authors.lastname: Lu
authors.affiliation: Departments of Pathology, Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China. Electronic address: jmying@hotmail.com.
authors.forename: Jianming
authors.initials: J
authors.lastname: Ying
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality*; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D005784:Gene Amplification; D015870:Gene Expression; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D012307:Risk Factors; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D066246:ErbB Receptors
keywords: Epidermal growth factor receptor; Gene amplification; Lung adenocarcinoma; Mutation; Tumor heterogeneity; Tyrosine kinase inhibitor