title: Epidermal growth factor receptor mutations in small cell lung cancer.
abstract: OBJECTIVE
  The vast majority of epidermal growth factor receptor (EGFR) mutations occur in lung adenocarcinoma, and even rare cases of other subtypes with this mutation, such as adenosquamous cell carcinoma, are associated with adenocarcinoma histology. According to this adenocarcinoma-specific nature of EGFR mutation, analysis of EGFR mutations with small cell lung cancers (SCLC) may provide a clue to its histogenesis.
  
  
  METHODS
  The mutational status of the EGFR gene was accessed in a cohort of 122 patients with SCLC; all patients were from a single institute. When the EGFR mutated, its gene copy number was also examined.
  
  
  RESULTS
  EGFR mutations were detected in five SCLCs (4%). The patients were mainly in the light smoker and histologic combined subtype. All but one of the tumors harbored gene amplifications. Notably, in three tumors of the combined SCLC subtype, both components of adenocarcinoma and SCLC harbored an EGFR mutation, whereas gene amplification was detected only in the adenocarcinoma component. A partial response was achieved in a patient (with an EGFR mutation) who was treated with gefitinib.
  
  
  CONCLUSIONS
  Although EGFR mutations are rare in SCLC, a combined subtype of SCLC with adenocarcinoma in light smokers may have a chance of harboring EGFR mutations. For patients with an EGFR mutation, EGFR tyrosine kinase inhibitor can be a treatment option. In terms of molecular pathogenesis, it is suggested that some SCLCs may have developed from pre-existing adenocarcinomas with EGFR mutations, but the development may not be simply linear, taking into consideration the discordant distribution of EGFR amplification.
authors.affiliation: Department of Pathology, Aichi Cancer Center Hospital, Kanokoden, Chukusa-ku, Nagoya, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Tatematsu
authors.forename: Junichi
authors.initials: J
authors.lastname: Shimizu
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Murakami
authors.forename: Yoshitsugu
authors.initials: Y
authors.lastname: Horio
authors.forename: Shigeo
authors.initials: S
authors.lastname: Nakamura
authors.forename: Toyoaki
authors.initials: T
authors.lastname: Hida
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Mitsudomi
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Yatabe
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004252:DNA Mutational Analysis; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066246:ErbB Receptors / Q000235:genetics* / Q000502:physiology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018773:Genes, erbB-1; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D055752:Small Cell Lung Carcinoma / Q000235:genetics* / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases