Comparison of epidermal growth factor receptor mutation statuses in tissue and plasma in stage I-IV non-small cell lung cancer patients

Respiration. 2013;85(2):119-25. doi: 10.1159/000338790. Epub 2012 Jul 10.


Background: Epidermal growth factor receptor (EGFR) mutations play essential roles in the treatment of non-small cell lung cancer (NSCLC) patients using EGFR tyrosine kinase inhibitors. Detection of EGFR mutations in blood cell-free DNA (cfDNA) seems promising. However, the mutation status in the plasma/serum is not always consistent with that in the tissues.

Objectives: The aims of this study were to compare the mutation statuses in plasma to those in tissues and thus to determine the specific subgroups of NSCLC patients who may be the best candidates for EGFR mutation analyses using blood cfDNA.

Methods: A total of 111 pairs of tissue and plasma samples were collected. Mutant-enriched PCR and sequencing analyses were performed to detect EGFR exon 19 deletions and exon 21 L858R mutations.

Results: Mutations were discovered in 43.2% (48/111) of the patients. The overall rate of consistency of the EGFR mutation statuses for the 111 paired plasma and tissue samples was 71.2% (79/111). The sensitivity and specificity rates of detecting EGFR mutations in the plasma were 35.6% (16/45) and 95.5% (63/66), respectively. The disease stage and tumor differentiation subgroups showed significantly different detection sensitivities; the sensitivity was 10% in early-stage patients and 56% in advanced-stage patients (p = 0.0014). For patients with poorly differentiated tumors, the sensitivity was 77.8%, which was significantly different from those with highly differentiated (20%; p = 0.0230) and moderately differentiated tumors (19%; p = 0.0042).

Conclusion: Blood analyses for EGFR mutations may be effectively used in advanced-stage patients or patients with poorly differentiated tumors.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • DNA Mutational Analysis / methods
  • ErbB Receptors / genetics*
  • ErbB Receptors / metabolism
  • Exons / genetics
  • Female
  • Humans
  • Lung / metabolism
  • Lung / pathology
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Mutation*
  • Polymerase Chain Reaction
  • Sensitivity and Specificity


  • ErbB Receptors