title: A correlation between EGFR gene mutation status and bronchioloalveolar carcinoma features in Japanese patients with adenocarcinoma.
abstract: BACKGROUND
  The presence of epidermal growth factor receptor (EGFR) mutations in gefitinib-naive lung cancer patients has been reported to be higher in females, in non-smokers, in Japanese, and in adenocarcinoma patients, especially in bronchioloalveolar carcinoma (BAC). To further investigate the prevalence of EGFR mutations in relation to pathological factors, we evaluated EGFR mutations in series of Japanese adenocarcinoma patients who had never been treated with gefitinib.
  
  
  METHODS
  In the previous studies, we examined mutation status in the tyrosine kinase domain of EGFR, exon18 through exon21, in 112 primary lung adenocarcinoma samples. Using these data, adenocarcinomas were histologically classified according to the presence or absence of bronchioloalveolar components.
  
  
  RESULTS
  Among 112 patients, 48 had adenocarcinoma with BAC components. Those with adenocarcinomas with BAC components had higher frequency of EGFR mutation (28/48, 58%) than those with non-BAC adenocarcinoma (24/64, 37%, P = 0.036). Male patients had the same trend; 12/23 (52%) male patients with adenocarcinoma with BAC components and 10/47 (21%) of those with non-BAC adenocarcinoma had EGFR mutation (P = 0.0135) but there was no correlation between the EGFR mutation status and with/without BAC components in 42 female patients (P = 0.30). Among 11 male non-smokers, patients with adenocarcinoma with BAC components had a tendency to have EGFR mutation more frequently than those with non-BAC adenocarcinoma (P = 0.061). In clear contrast, the frequency of EGFR mutation did not differ significantly between male smoker patients with adenocarcinoma with BAC components and those with non-BAC. Among patients with adenocarcinoma with BAC components, those with adenocarcinoma with EGFR gene mutation had a significantly better 5 year survival than those with adenocarcinoma with wild-type (85.7 versus 46.0%, P = 0.0017).
  
  
  CONCLUSIONS
  Adenocarcinomas with BAC components in male non-smokers seem to predict the presence of EGFR mutation. Half of female adenocarcinoma patients with EGFR mutation exhibit adenocarcinomas with non-BAC suggesting a different behavior from those in males. The prognosis of patients with adenocarcinoma with BAC components with EGFR gene mutation is predicted to be better than that of patients with adenocarcinoma with BAC components with wild-type EGFR gene.
authors.affiliation: Department of Surgery II, Nagoya City University Medical School, Mizuho-ku, Nagoya 467-8601, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Haneda
authors.forename: Hidefumi
authors.initials: H
authors.lastname: Sasaki
authors.forename: Neal
authors.initials: N
authors.lastname: Lindeman
authors.forename: Osamu
authors.initials: O
authors.lastname: Kawano
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Endo
authors.forename: Eriko
authors.initials: E
authors.lastname: Suzuki
authors.forename: Shigeki
authors.initials: S
authors.lastname: Shimizu
authors.forename: Haruhiro
authors.initials: H
authors.lastname: Yukiue
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: Motoki
authors.initials: M
authors.lastname: Yano
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Fujii
mesh_terms: D000230:Adenocarcinoma / Q000145:classification / Q000235:genetics* / Q000473:pathology; D002282:Adenocarcinoma, Bronchiolo-Alveolar / Q000145:classification / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D020440:Gene Duplication; D006801:Humans; D007564:Japan; D008175:Lung Neoplasms / Q000145:classification / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011237:Predictive Value of Tests; D012189:Retrospective Studies
chemical_list: D066246:ErbB Receptors