title: Analysis of intratumor heterogeneity of EGFR mutations in mixed type lung adenocarcinoma.
abstract: BACKGROUND
  Epidermal growth factor receptor mutations are predictive of the success of EGFR tyrosine kinase inhibitor treatment in patients with advanced non--small-cell lung cancer. As with other solid tumors, lung cancer is thought to be the result of an accumulation of genetic alterations after exposure to carcinogens. The aim of the present study was to clarify the relationship between multistep carcinogenesis and the accumulation of EGFR mutations.
  
  
  METHODS
  The intratumor heterogeneity of EGFR mutations was analyzed in 38 patients with resected mixed-type lung adenocarcinoma according to histological patterns, and the clinical features of the patients harboring intratumor heterogeneity of EGFR mutations were evaluated.
  
  
  RESULTS
  Intratumor heterogeneity of EGFR mutations was detected in 9 of 38 tumors. EGFR mutations were more common in the bronchioloalveolar (lepidic) carcinoma pattern than in the papillary and acinar patterns, although this difference was not significant. However, there was a significant correlation between intratumor heterogeneity of EGFR mutations and smoking history (P < .043).
  
  
  CONCLUSIONS
  Intratumor heterogeneity of EGFR mutations correlates with the distribution of histological subtype in mixed type adenocarcinoma and is associated with smoking history.
authors.affiliation: Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki, Japan.
authors.forename: Nanae
authors.initials: N
authors.lastname: Tomonaga
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yamaguchi
authors.forename: Takaya
authors.initials: T
authors.lastname: Ikeda
authors.forename: Kosuke
authors.initials: K
authors.lastname: Mizoguchi
authors.forename: Kohei
authors.initials: K
authors.lastname: Motoshima
authors.forename: Seiji
authors.initials: S
authors.lastname: Doi
authors.forename: Katsumi
authors.initials: K
authors.lastname: Nakatomi
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Iida
authors.forename: Tomayoshi
authors.initials: T
authors.lastname: Hayashi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nagayasu
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Tsukamoto
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kohno
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D002282:Adenocarcinoma, Bronchiolo-Alveolar / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D002291:Carcinoma, Papillary / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D004273:DNA, Neoplasm / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D061346:Laser Capture Microdissection; D008175:Lung Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D011379:Prognosis; D012907:Smoking / Q000009:adverse effects; D015996:Survival Rate
chemical_list: D004273:DNA, Neoplasm; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: EGFR mutations; Heterogeneity; Mixed type adenocarcinoma; Non–small-cell lung cancer; Smoking