Abnormalities of epidermal growth factor receptor in lung squamous-cell carcinomas, adenosquamous carcinomas, and large-cell carcinomas: tyrosine kinase domain mutations are not rare in tumors with an adenocarcinoma component

Cancer. 2007 Feb 15;109(4):741-50. doi: 10.1002/cncr.22476.


Background: Tyrosine kinase domain (TKD) gene mutations of the epidermal growth factor receptor gene (EGFR) have proven to be clinically significant in nonsmall-cell lung cancer (NSCLC), particularly in adenocarcinoma. However, TKD mutations together with deletion mutations in the extracellular domain of EGFR (EGFRvIII) have not been fully investigated in NSCLC except for adenocarcinoma. The present study sought to gain further insight into the significance of EGFR mutations in NSCLC by focusing on nonadenocarcinoma NSCLC.

Methods: EGFR TKD mutations were investigated using direct sequencing and mutation-specific polymerase chain reaction (PCR), and EGFRvIII mutations were examined using reverse transcriptase-PCR in samples from 42 NSCLC patients and 6 NSCLC cell lines excluding adenocarcinoma.

Results: EGFR TKD mutations were detected in 1 of 7 (14%) squamous-cell carcinomas with an adenocarcinoma component and 2 of 4 (50%) adenosquamous carcinomas. In contrast, EGFR TKD mutations were not identified in 24 pure squamous-cell carcinomas without any adenocarcinoma component, 7 large-cell carcinomas, or 6 cell lines. EGFRvIII was detected solely in 1 of 7 large-cell carcinomas (14%), but not in 31 squamous-cell carcinomas, 4 adenosquamous carcinomas, or 6 cell lines.

Conclusions: These results suggest that EGFR TKD mutations are found in NSCLCs with an adenocarcinoma element. Patients with such lesions are thus considered candidates for molecular therapies targeting EGFR.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Adenosquamous / drug therapy
  • Carcinoma, Adenosquamous / genetics*
  • Carcinoma, Large Cell / drug therapy
  • Carcinoma, Large Cell / genetics*
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Squamous Cell / drug therapy
  • Carcinoma, Squamous Cell / genetics*
  • DNA Mutational Analysis
  • ErbB Receptors / genetics*
  • Female
  • Humans
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / genetics
  • Male
  • Middle Aged
  • Mutation*
  • Neoplasm Staging
  • Prognosis
  • Protein Structure, Tertiary
  • Protein-Tyrosine Kinases / chemistry
  • Survival Rate


  • epidermal growth factor receptor VIII
  • ErbB Receptors
  • Protein-Tyrosine Kinases