Comparison of EGFR and K-RAS gene status between primary tumours and corresponding metastases in NSCLC

Br J Cancer. 2008 Sep 16;99(6):923-9. doi: 10.1038/sj.bjc.6604629.


In non-small-cell lung cancer (NSCLC), epidermal growth factor receptor (EGFR) and K-RAS mutations of the primary tumour are associated with responsiveness and resistance to tyrosine kinase inhibitors (TKIs), respectively. However, the EGFR and K-RAS mutation status in metastases is not well studied. We compared the mutation status of these genes between the primary tumours and the corresponding metastases of 25 patients. Epidermal growth factor receptor and K-RAS mutation status was different between primary tumours and corresponding metastases in 7 (28%) and 6 (24%) of the 25 patients, respectively. Among the 25 primary tumours, three 'hotspot' and two non-classical EGFR mutations were found; none of the corresponding metastases had the same mutation pattern. Among the five (20%) K-RAS mutations detected in the primary tumours, two were maintained in the corresponding metastasis. Epidermal growth factor receptor and K-RAS mutations were detected in the metastatic tumours of three (12%) and five (20%) patients, respectively. The expressions of EGFR and phosphorylated EGFR showed I 0 and 50% discordance, in that order. We conclude that there is substantial discordance in EGFR and K-RAS mutational status between the primary tumours and corresponding metastases in patients with NSCLC and this might have therapeutic implications when treatment with TKIs is considered.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / secondary
  • Adult
  • Aged
  • Biomarkers, Tumor
  • Carcinoma, Giant Cell / genetics
  • Carcinoma, Giant Cell / secondary
  • Carcinoma, Large Cell / genetics
  • Carcinoma, Large Cell / secondary
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / secondary*
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / secondary
  • ErbB Receptors / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunoenzyme Techniques
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Mutation
  • Neoplasm Recurrence, Local
  • Neoplasm Staging
  • Phosphorylation
  • Polymerase Chain Reaction
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins p21(ras)
  • Retrospective Studies
  • ras Proteins / genetics*


  • Biomarkers, Tumor
  • KRAS protein, human
  • Proto-Oncogene Proteins
  • EGFR protein, human
  • ErbB Receptors
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins