title: L858R EGFR mutation status correlated with clinico-pathological features of Japanese lung cancer.
abstract: Somatic mutations of the epidermal growth factor receptor (EGFR) gene were found in about 25-40% of Japanese lung cancer patients. These mutations are associated with clinical and radiographic responses to EGFR tyrosine kinase inhibitors. Most common mutation are arginine for leucine substitution at amino acid 858 (L858R) and exon 19 deletions, especially deletion type 1 mutation. We investigated these EGFR mutation statuses in 575 surgically treated non-small cell lung cancer (NSCLC) cases. Three-hundred and sixty-two adenocarcinoma cases were included. The presence or absence of EGFR mutations of kinase domains was analyzed by genotyping analysis (TaqMan assay; n=386, and LightCycler assay; n=98) and sequences (n=91). EGFR mutations (CTG; CGG; L858R) were found from 63 of 575 lung cancer patients. We also detected the deletion 1a type mutations (2235-2249 del GGAATTAAGAGAAGC) from 39 patients and deletion 1b type mutations (2236-2250 del GAATTAAGAGAAGCA) from 15 patients in exon 19. These mutation statuses were significantly correlated with gender, smoking status (never smoker versus smoker), and pathological subtypes (adenocarcinoma versus non-adenocarcinoma). L858R mutation (p<0.0001), but not deletion 1 type mutation (p=0.0665), was correlated with differentiation status (well versus moderately or poorly) of lung cancers. L858R mutation ratio was significantly higher in non-smoker (p=0.0496) and adenocaicinoma (p=0.0136) when compared to deletion 1 type mutations. The EGFR mutation status, especially L858R mutation might be correlated with the clinico-pathological features related to good response to gefitinib, such as gender, smoking history, and pathological subtypes of Japanese lung cancers.
authors.affiliation: Department of Surgery II, Nagoya City University Medical School, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan. hisasaki@med.nagoya-cu.ac.jp
authors.forename: Hidefumi
authors.initials: H
authors.lastname: Sasaki
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Endo
authors.forename: Minoru
authors.initials: M
authors.lastname: Takada
authors.forename: Masaaki
authors.initials: M
authors.lastname: Kawahara
authors.forename: Naoto
authors.initials: N
authors.lastname: Kitahara
authors.forename: Hisaichi
authors.initials: H
authors.lastname: Tanaka
authors.forename: Meinoshin
authors.initials: M
authors.lastname: Okumura
authors.forename: Akihide
authors.initials: A
authors.lastname: Matsumura
authors.forename: Keiji
authors.initials: K
authors.lastname: Iuchi
authors.forename: Tomoya
authors.initials: T
authors.lastname: Kawaguchi
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 / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D066246:ErbB Receptors / Q000235:genetics*; D005091:Exons; D005260:Female; D000077156:Gefitinib; D005838:Genotype; D006801:Humans; D007564:Japan; D016014:Linear Models; D008175:Lung Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011799:Quinazolines / Q000494:pharmacology; D018709:Statistics, Nonparametric; D015996:Survival Rate
chemical_list: D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D066246:ErbB Receptors; D000077156:Gefitinib