title: Clinicopathologic significance of the mutations of the epidermal growth factor receptor gene in patients with non-small cell lung cancer.
abstract: OBJECTIVE
  It has been reported that the mutations of epidermal growth factor receptor (EGFR) are detected in lung cancers. Studies of EGFR mutations in large numbers of patients' tumors with clinical data including response to EGFR tyrosine kinase directed therapy are needed to develop a robust database for clinical use. The purpose of the present study is to gain further insights into the significance of EGFR mutation in non-small cell lung cancer (NSCLC).
  
  
  METHODS
  We investigated the clinicopathologic significance of tyrosine kinase domain (exons 18-21) EGFR mutations in 120 patients with primary NSCLC and the correlation between EGFR mutation and sensitivity to gefitinib in an additional 20 NSCLC patients treated with gefitinib. In addition, onocogenic KRAS mutations and RASSF1A promoter methylation were determined in the same samples.
  
  
  RESULTS
  EGFR mutation was detected in 29 of 120 (24%) tumors. All of the 29 (40%) mutations occurred in 72 adenocarcinomas. EGFR mutation was significantly more frequent in females (47%) than males (12%, P < 0.0001), in younger patients (38%) than older patients (10%, P = 0.0005), in nonsmokers (47%) than smokers (13%, P < 0.0001), and in well-differentiated tumors (39%) than moderately and poorly differentiated tumors (7%, P < 0.0001). Mutation of the EGFR gene was preferentially observed in advanced disease. Furthermore, EGFR mutations were detected in 11 of 14 (79%) responders, whereas none of six (0%) nonresponders had the mutation (P = 0.0022).
  
  
  CONCLUSIONS
  These results in Japanese (East Asian) patients indicated that EGFR mutation plays an important role in pathogenesis of lung adenocarcinoma.
authors.affiliation: Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Showa-machi, Maebashi, Gunma, Japan. ytomizaw@showa.gunma-u.ac.jp
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Tomizawa
authors.forename: Hironobu
authors.initials: H
authors.lastname: Iijima
authors.forename: Noriaki
authors.initials: N
authors.lastname: Sunaga
authors.forename: Koji
authors.initials: K
authors.lastname: Sato
authors.forename: Atsushi
authors.initials: A
authors.lastname: Takise
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Otani
authors.forename: Shigefumi
authors.initials: S
authors.lastname: Tanaka
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Suga
authors.forename: Ryusei
authors.initials: R
authors.lastname: Saito
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Ishizuka
authors.forename: Kunio
authors.initials: K
authors.lastname: Dobashi
authors.forename: John D
authors.initials: JD
authors.lastname: Minna
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakajima
authors.forename: Masatomo
authors.initials: M
authors.lastname: Mori
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis / Q000235:genetics*; D002454:Cell Differentiation; D019175:DNA Methylation; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000737:chemistry; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D005091:Exons; D005260:Female; D000077156:Gefitinib; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011401:Promoter Regions, Genetic; D017434:Protein Structure, Tertiary; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism; D011799:Quinazolines / Q000494:pharmacology; D012907:Smoking; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: D017931:DNA Primers; D011799:Quinazolines; C411762:RASSF1 protein, human; D025521:Tumor Suppressor Proteins; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras); D000077156:Gefitinib