Circulating EGFR Mutations in Patients with Lung Adenocarcinoma by Circulating Tumor Cell Isolation Systems: A Concordance Study

Int J Mol Sci. 2022 Sep 13;23(18):10661. doi: 10.3390/ijms231810661.

Abstract

Background: We developed a hybrid platform using a negative combined with a positive selection strategy to capture circulating tumor cells (CTCs) and detect epidermal growth factor receptor (EGFR) mutations in patients with metastatic lung adenocarcinoma. Methods: Blood samples were collected from patients with pathology-proven treatment-naïve stage IV lung adenocarcinoma. Genomic DNA was extracted from CTCs collected for EGFR mutational tests. The second set of CTC-EGFR mutational tests were performed after three months of anti-cancer therapy. Results: A total of 80 samples collected from 28 patients enrolled between July 2016 and August 2018. Seventeen patients had EGFR mutations, including Exon 19 deletion (n = 11), L858R (n = 5), and de-novo T790 and L858R (n = 1). Concordance between tissue and CTCs before treatment was 88.2% in EGFR- mutant patients and 90.9% in non-mutant patients. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of EGFR mutation tests for CTCs were 89.3%, 88.2%, 90.9%, 93.8%, and 83.3%, respectively. Conclusions: CTCs captured by a hybrid platform using a negative and positive selection strategy may serve as a suitable and reliable source of lung cancer tumor DNA for detecting EGFR mutations, including T790M.

Keywords: EGFR mutation; circulating tumor cells; liquid biopsy; lung adenocarcinoma.

MeSH terms

  • Adenocarcinoma of Lung* / genetics
  • ErbB Receptors / genetics*
  • Humans
  • Lung Neoplasms* / pathology
  • Mutation
  • Neoplastic Cells, Circulating* / pathology
  • Protein Kinase Inhibitors

Substances

  • Protein Kinase Inhibitors
  • EGFR protein, human
  • ErbB Receptors