title: Epidemiological study of HER-2 mutations among EGFR wild-type lung adenocarcinoma patients in China.
abstract: Human epidermal growth factor receptor (HER)-2 is a driver gene in non-small cell lung cancer (NSCLC). The present study evaluated the mutation rate of HER-2 within the wild-type epidermal growth factor receptor (EGFR) lung adenocarcinoma population in China.
  
  
  
  Formalin-fixed, paraffin-embedded samples from 456 patients with wild-type EGFR lung adenocarcinoma were analyzed for HER-2 mutations by amplification-refractory mutation system (ARMS), and HER-2 protein expression was evaluated by immunohistochemistry. All samples positive for HER-2 mutation underwent direct sequencing for further verification.
  
  
  
  HER-2 mutation was detected in 22/456 cases (4.8 %); the rate was 6.7 % among 331 triple-negative samples (i.e., wild-type EGFR, anaplastic lymphoma kinase, and ROS proto-oncogene 1). Direct sequencing confirmed that the results were consistent with those obtained by ARMS analysis in 19 cases. The positive rate was 15.4 % by immunohistochemical analysis of HER-2 expression; this was not correlated with mutation rate. HER-2 mutation and positivity were not correlated with gender, age, smoking status, disease stage, or histological subtype. The 22 cases of HER-2 mutations occurred only in acinar (36.4 %), papillary (36.4 %), minimally invasive (13.6 %), solid (9.2 %), and invasive mucinous (4.5 %) subtypes. Disease-free and overall survival were not associated with HER-2 mutation or HER-2 protein overexpression.
  
  
  
  The HER-2 mutation rate was 4.8 % among EGFR wild-type lung adenocarcinoma patients in China, and 6.7 % among driver genes, triple-negative lung adenocarcinoma. The incidence of HER-2 mutation varied among different lung adenocarcinoma subtypes, occurring mainly in acinar and papillary predominant subtypes. 15.4 % of EGFR wild-type lung adenocarcinoma patients showed HER-2 protein overexpression, but this was not correlated to HER-2 mutation. Existing follow-up data did not show a correlation between HER-2 mutation with DFS or OS.
authors: Department of Lung Cancer and Immunology, Shanghai Pulmonary Hospital, Tongji University, No. 507 Zhengmin Road, Shanghai, 200433, People's Republic of China.
authors: Xuefei
authors: X
authors: Li
authors: Department of Lung Cancer and Immunology, Shanghai Pulmonary Hospital, Tongji University, No. 507 Zhengmin Road, Shanghai, 200433, People's Republic of China.
authors: Chao
authors: C
authors: Zhao
authors: Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University Medical School Cancer Institute, Tongji University School of Medicine, No. 507 Zhengmin Road, Shanghai, 200433, People's Republic of China.
authors: Chunxia
authors: C
authors: Su
authors: Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University Medical School Cancer Institute, Tongji University School of Medicine, No. 507 Zhengmin Road, Shanghai, 200433, People's Republic of China.
authors: Shengxiang
authors: S
authors: Ren
authors: Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University Medical School Cancer Institute, Tongji University School of Medicine, No. 507 Zhengmin Road, Shanghai, 200433, People's Republic of China.
authors: Xiaoxia
authors: X
authors: Chen
authors: Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University Medical School Cancer Institute, Tongji University School of Medicine, No. 507 Zhengmin Road, Shanghai, 200433, People's Republic of China. caicunzhoudr@163.com.
authors: Caicun
authors: C
authors: Zhou
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics* / Q000401:mortality; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000077548:Anaplastic Lymphoma Kinase; D014408:Biomarkers, Tumor; D002681:China / Q000453:epidemiology; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009154:Mutation; D059645:Mutation Rate; D009367:Neoplasm Staging; D011159:Population Surveillance; D011379:Prognosis; D000090063:Proto-Oncogene Mas; D020794:Receptor Protein-Tyrosine Kinases; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D016019:Survival Analysis
chemical_list: D000077548:Anaplastic Lymphoma Kinase; D014408:Biomarkers, Tumor; D066246:ErbB Receptors; D000090063:Proto-Oncogene Mas; D020794:Receptor Protein-Tyrosine Kinases; D018719:Erb-b2 Receptor Tyrosine Kinases; C000715470:MAS1 protein, human; C000626173:ALK protein, human
keywords: ALK; HER-2; Lung adenocarcinoma; ROS1