title: Correlation of EGFR mutation status with predominant histologic subtype of adenocarcinoma according to the new lung adenocarcinoma classification of the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society.
abstract: BACKGROUND
  Epidermal growth factor receptor (EGFR) mutations have been identified as predictors of response to EGFR tyrosine kinase inhibitors in non-small cell lung cancer.
  
  
  OBJECTIVE
  To investigate the relationship of EGFR mutation status to the histologic subtype of adenocarcinoma according to the new International Association for the Study of Lung Cancer (IASLC)/American Thoracic Society (ATS)/European Respiratory Society (ERS) classification.
  
  
  METHODS
  We screened EGFR mutation in 200 consecutive lung adenocarcinoma resection specimens diagnosed between 2008 and 2011.
  
  
  RESULTS
  Among 200 lung adenocarcinomas, EGFR mutations were identified in 41 tumors (20.5%). The mean age in the EGFR-mutant group was 64.8 years and this group consisted of 78% females and 22% males. Most patients with EGFR-positive lung cancers were never-smokers (51%) as compared to 8% with EGFR-negative cancers (P < .001). The most common mutations identified in our population were deletions in exon 19 (22 patients) and L858R in exon 21 (12 patients). Five patients had double mutations. The predominant pattern of adenocarcinoma was lepidic (44%) in EGFR-mutant lung cancers as compared to 69% with acinar pattern in EGFR wild-type lung cancers (P < .001). Of 22 minimally invasive adenocarcinomas, 8 (36%) had EGFR mutations, accounting for 20% of adenocarcinomas with EGFR mutations (P < .05).
  
  
  CONCLUSIONS
  Based on the new IASLC/ATS/ERS classification, the predominant subtype of adenocarcinoma was lepidic (44%) in EGFR-mutant lung cancers (P < .001). However, histologic subtype should not be used to exclude patients from tyrosine kinase inhibitor therapy, since EGFR mutations are found in lung adenocarcinomas of other subtypes.
authors.affiliation: From the Department of Pathology (Drs Villa, Yeldandi, and Raparia), the Division of Medical Oncology, and Robert H. Lurie Comprehensive Cancer Center (Drs Johnson and Patel), the Division of Pulmonary, and Critical Care Medicine (Dr Raj); and the Division of Thoracic Surgery, and Robert H. Lurie Comprehensive Cancer Center (Dr DeCamp), Northwestern University Feinberg School of Medicine, Chicago, Illinois; and the Department of Pathology & Genomic Medicine, The Methodist Hospital, Houston, Texas (Dr Cagle).
authors.forename: Celina
authors.initials: C
authors.lastname: Villa
authors.forename: Philip T
authors.initials: PT
authors.lastname: Cagle
authors.forename: Melissa
authors.initials: M
authors.lastname: Johnson
authors.forename: Jyoti D
authors.initials: JD
authors.lastname: Patel
authors.forename: Anjana V
authors.initials: AV
authors.lastname: Yeldandi
authors.forename: Rishi
authors.initials: R
authors.lastname: Raj
authors.forename: Malcolm M
authors.initials: MM
authors.lastname: DeCamp
authors.forename: Kirtee
authors.initials: K
authors.lastname: Raparia
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019943:Amino Acid Substitution; D002641:Chicago; D066246:ErbB Receptors / Q000235:genetics*; D005062:European Union; D005260:Female; D005500:Follow-Up Studies; D017353:Gene Deletion; D056726:Genetic Association Studies; D006801:Humans; D007390:International Agencies; D008168:Lung / Q000473:pathology*; D008175:Lung Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D017410:Practice Guidelines as Topic; D011379:Prognosis; D012955:Societies, Medical; D012958:Societies, Scientific; D014481:United States; D014837:Voluntary Health Agencies
chemical_list: C512478:EGFR protein, human; D066246:ErbB Receptors