title: The relationship between epidermal growth factor receptor mutations and clinicopathologic features in non-small cell lung cancers.
abstract: OBJECTIVE
  Recent studies reported that clinical responsiveness to gefitinib was associated with somatic mutation of epidermal growth factor receptor (EGFR) gene in non-small cell lung cancers (NSCLC). Here, we investigated the relationship between EGFR mutation and clinicopathologic features.
  
  
  METHODS
  EGFR mutational status of 120 NSCLCs was determined mainly in EGFR exons 18 to 21 by direct sequence and correlated with clinicopathologic parameters.
  
  
  RESULTS
  EGFR mutations were present in 38 cases (32%) and the majority of mutations were in-frame deletions of exon 19 (19 cases) and a missense mutation in exon 21 (18 cases). EGFR mutations were frequently associated with adenocarcinoma (P < 0.0001), never smoker (P < 0.0001), and female gender (P = 0.0001). Of interest, increasing smoke exposure was inversely related to the rate of EGFR mutation (P < 0.0001). Multivariate analysis showed that smoking and histology were independent variables. Furthermore, gender difference was observed for the mutational location (P = 0.01) dominance of exon 19 for males and exon 21 for females. Twenty-one cases were treated with gefitinib and found that EGFR mutation was significantly related to gefitinib responsiveness (P = 0.002). In addition, median survival times of patients with and without EGFR mutations treated with gefitinib were 25.1 and 14.0 months, respectively. Patients with EGFR mutations had approximately 2-fold survival advantage; however, the difference was not significant.
  
  
  CONCLUSIONS
  We show that EGFR mutations were significantly related to histology and smoke exposure and were a strong predictive factor for gefitinib responsiveness in NSCLC.
authors.affiliation: Department of Cancer and Thoracic Surgery, Graduate School of Medicine and Dentistry, Okayama University, 2-5-1 Shikata-cho, Okayama 700-8558, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Tokumo
authors.forename: Shinichi
authors.initials: S
authors.lastname: Toyooka
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Kiura
authors.forename: Hisayuki
authors.initials: H
authors.lastname: Shigematsu
authors.forename: Kunitoshi
authors.initials: K
authors.lastname: Tomii
authors.forename: Motoi
authors.initials: M
authors.lastname: Aoe
authors.forename: Kouichi
authors.initials: K
authors.lastname: Ichimura
authors.forename: Toshihide
authors.initials: T
authors.lastname: Tsuda
authors.forename: Masaaki
authors.initials: M
authors.lastname: Yano
authors.forename: Kazunori
authors.initials: K
authors.lastname: Tsukuda
authors.forename: Masahiro
authors.initials: M
authors.lastname: Tabata
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ueoka
authors.forename: Mitsune
authors.initials: M
authors.lastname: Tanimoto
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Date
authors.forename: Adi F
authors.initials: AF
authors.lastname: Gazdar
authors.forename: Nobuyoshi
authors.initials: N
authors.lastname: Shimizu
mesh_terms: D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001483:Base Sequence; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011799:Quinazolines / Q000627:therapeutic use; D017386:Sequence Homology, Amino Acid; D012907:Smoking; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D011799:Quinazolines; D066246:ErbB Receptors; D000077156:Gefitinib