Identification of circulating tumor cells using 4-color fluorescence in situ hybridization: Validation of a noninvasive aid for ruling out lung cancer in patients with low-dose computed tomography-detected lung nodules

Cancer Cytopathol. 2020 Aug;128(8):553-562. doi: 10.1002/cncy.22278. Epub 2020 Apr 22.

Abstract

Background: Approximately one third of needle biopsies that are performed to rule out malignancy of indeterminate pulmonary nodules detected radiologically during lung cancer screening are negative, thus exposing cancer-free patients to risks of pneumothorax, bleeding, and infection. A noninvasive confirmatory tool (eg, liquid biopsy) is urgently needed in the lung cancer diagnosis setting to stratify patients who should receive biopsy versus those who should be monitored.

Methods: A novel antigen-independent, 4-color fluorescence in situ hybridization (FISH)-based method was developed to detect circulating tumor cells (CTCs) with abnormalities in gene copy numbers in mononuclear cell-enriched peripheral blood samples from patients with (n = 107) and without (n = 100) lung cancer.

Results: Identification of CTCs using FISH probes at 10q22.3/CEP10 and 3p22.1/3q29 detected lung cancer cases with 94.2% accuracy, 89% sensitivity, and 100% specificity compared with biopsy.

Conclusion: The high accuracy of this liquid biopsy method suggests that it may be used as a noninvasive decision tool to reduce the frequency of unnecessary needle biopsy in patients with benign pulmonary lesions.

Keywords: CTC; FISH; LDCT screening; indeterminate lung nodules; lung cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • A549 Cells
  • Aged
  • Aneuploidy
  • Diagnosis, Differential
  • Female
  • Humans
  • In Situ Hybridization, Fluorescence / methods
  • Liquid Biopsy
  • Lung Diseases / diagnosis*
  • Lung Diseases / diagnostic imaging
  • Lung Diseases / genetics
  • Lung Neoplasms / diagnosis*
  • Lung Neoplasms / diagnostic imaging
  • Lung Neoplasms / genetics
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Neoplastic Cells, Circulating*
  • Sensitivity and Specificity
  • Tomography, X-Ray Computed / methods*