Comparison between epidermal growth factor receptor (EGFR) gene expression in primary non-small cell lung cancer (NSCLC) and in fine-needle aspirates from distant metastatic sites

J Thorac Oncol. 2008 Jan;3(1):18-22. doi: 10.1097/JTO.0b013e31815e8ba2.


Purpose: Epidermal growth factor receptor (EGFR) gene copy number obtained by fluorescence in situ hybridization (FISH) has been recently found to predict treatment outcome in non-small cell lung cancer (NSCLC) patients receiving EGFR tyrosine kinase inhibitors. However, it is still unknown whether EGFR status differs in metastases compared with primary NSCLC. In all studies FISH have been performed on histologic material. The possibility to perform FISH analysis on cytologic material obtained by fine-needle aspiration from superficial and visceral metastases would allow us to know the real EGFR status avoiding invasive diagnostic procedures.

Methods: EGFR gene copy number was analyzed by FISH on fine-needle aspirates obtained from 31 patients with metastatic NSCLC and the results were compared with those obtained on corresponding paraffin histologic sections from the primary tumor.

Results: The feasibility of EGFR FISH on cytology was 90% (28 of 31 patients). EGFR FISH was positive in 61% (17 of 28 patients) of the metastases and in 36% (10 of 28 patients) of the primary tumors. Nine of the 28 cases (32%) were EGFR positive on both primary tumor and metastatic site and 10 (36%) were negative on both primary tumor and metastasis. Nine of the 28 cases (32%) showed discordance of primary tumor versus metastasis (McNemar test; p = 0.041).

Conclusions: EGFR FISH can be reliably assessed on fine-needle aspirates obtained from NSCLC metastases. We found that EGFR gene copy number is discordant between primary NSCLC and the corresponding distant metastatic sites in a significant proportion of cases. These findings should be considered in future studies designed to elucidate the predictive role of EGFR FISH in NSCLC.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biopsy, Fine-Needle
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Carcinoma, Non-Small-Cell Lung / surgery
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / surgery
  • ErbB Receptors / genetics
  • ErbB Receptors / metabolism*
  • Feasibility Studies
  • Female
  • Gene Dosage
  • Humans
  • In Situ Hybridization, Fluorescence
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology*
  • Lung Neoplasms / surgery
  • Male
  • Middle Aged
  • Neoplasm Metastasis


  • ErbB Receptors