Epidermal growth factor receptor gene in primary tumor and metastatic sites from non-small cell lung cancer

J Thorac Oncol. 2009 Jun;4(6):684-8. doi: 10.1097/JTO.0b013e3181a52359.


Introduction: The majority of patients with non-small cell lung cancer (NSCLC) develop distant metastases. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors are capable of reducing brain and adrenal metastases. However, the EGFR status may be discordant between primary NSCLC and the corresponding metastases.

Methods: Using fluorescence in situ hybridization (FISH) analysis, the EGFR gene status was evaluated in a series of 38 cerebral or adrenal metastases collected from two institutions and in the corresponding primary tumors. Also, EGFR mutational analysis was performed using direct sequencing on the cerebral metastases.

Results: EGFR FISH was positive in 28% of the primary tumors and in 45% of the metastases (p < 0.05). Among the seven cases FISH-positive at the metastatic site but negative in the primary tumor, six were brain metastases, and one was an adrenal metastasis; all were polysomic for chromosome 7, none were amplified. No EGFR mutations have been found in the cerebral metastases.

Conclusion: Because the molecular asset of EGFR may change during the metastatic progression of NSCLC to brain (but not to adrenal), the selection of patients with brain metastasis for specific targeted therapies by EGFR FISH analysis should be performed on metastatic lesions rather than on their corresponding primary tumors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / secondary
  • Adrenal Gland Neoplasms / genetics*
  • Adrenal Gland Neoplasms / secondary
  • Aged
  • Aged, 80 and over
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / 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
  • Chromosomes, Human, Pair 7 / genetics
  • DNA, Neoplasm / genetics
  • DNA, Neoplasm / metabolism
  • ErbB Receptors / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • In Situ Hybridization, Fluorescence
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Prognosis
  • Small Cell Lung Carcinoma / genetics
  • Small Cell Lung Carcinoma / secondary
  • Survival Rate


  • DNA, Neoplasm
  • EGFR protein, human
  • ErbB Receptors