A rapid, sensitive assay to detect EGFR mutation in small biopsy specimens from lung cancer

J Mol Diagn. 2006 Jul;8(3):335-41. doi: 10.2353/jmoldx.2006.050104.

Abstract

It has been demonstrated that lung cancers, specifically a subset of pulmonary adenocarcinomas, with epidermal growth factor receptor (EGFR) mutation are highly sensitive to EGFR-targeted drugs. Therefore, a rapid, sensitive assay for mutation detection using routine pathological specimens is demanded in clinical practice to predict the response. We therefore developed a new assay for detecting EGFR mutation using only a paraffin section of a small biopsy specimen. The method was very sensitive, detecting as few as 5% cancer cells in a background of normal cells, the results usually being obtained within 4 hours. Furthermore, it was accurate, as shown by the high concordance with reverse transcriptase-polymerase chain reaction-coupled direct sequencing (186 of 195, 95%). The practical application of this assay to 29 cases treated with gefitinib resulted in a high prediction rate: 10 of the 11 responders were shown to be positive for the mutation, and all patients with progressive disease were negative. In addition, a mutation at codon 790, conferring gefitinib resistance, was successfully analyzed in a similar manner. In conclusion, the assay is a rapid, sensitive method using paraffin sections of biopsy specimens without a tumor cell-enrichment procedure and is quite useful to select a treatment of choice in clinical practice.

Publication types

  • Validation Study

MeSH terms

  • Biopsy / methods
  • DNA Mutational Analysis / methods*
  • Drug Resistance, Neoplasm / genetics
  • Drug Screening Assays, Antitumor / methods*
  • ErbB Receptors / genetics*
  • Female
  • Gefitinib
  • Humans
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / genetics*
  • Middle Aged
  • Models, Biological
  • Point Mutation*
  • Predictive Value of Tests
  • Quinazolines / therapeutic use
  • Sensitivity and Specificity
  • Treatment Failure

Substances

  • Quinazolines
  • ErbB Receptors
  • Gefitinib