"Sentinel" circulating tumor cells allow early diagnosis of lung cancer in patients with chronic obstructive pulmonary disease

PLoS One. 2014 Oct 31;9(10):e111597. doi: 10.1371/journal.pone.0111597. eCollection 2014.

Abstract

Chronic obstructive pulmonary disease (COPD) is a risk factor for lung cancer. Migration of circulating tumor cells (CTCs) into the blood stream is an early event that occurs during carcinogenesis. We aimed to examine the presence of CTCs in complement to CT-scan in COPD patients without clinically detectable lung cancer as a first step to identify a new marker for early lung cancer diagnosis. The presence of CTCs was examined by an ISET filtration-enrichment technique, for 245 subjects without cancer, including 168 (68.6%) COPD patients, and 77 subjects without COPD (31.4%), including 42 control smokers and 35 non-smoking healthy individuals. CTCs were identified by cytomorphological analysis and characterized by studying their expression of epithelial and mesenchymal markers. COPD patients were monitored annually by low-dose spiral CT. CTCs were detected in 3% of COPD patients (5 out of 168 patients). The annual surveillance of the CTC-positive COPD patients by CT-scan screening detected lung nodules 1 to 4 years after CTC detection, leading to prompt surgical resection and histopathological diagnosis of early-stage lung cancer. Follow-up of the 5 patients by CT-scan and ISET 12 month after surgery showed no tumor recurrence. CTCs detected in COPD patients had a heterogeneous expression of epithelial and mesenchymal markers, which was similar to the corresponding lung tumor phenotype. No CTCs were detected in control smoking and non-smoking healthy individuals. CTCs can be detected in patients with COPD without clinically detectable lung cancer. Monitoring "sentinel" CTC-positive COPD patients may allow early diagnosis of lung cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Early Detection of Cancer / methods*
  • Female
  • Humans
  • Immunohistochemistry
  • Lung Neoplasms / complications
  • Lung Neoplasms / diagnosis*
  • Lung Neoplasms / pathology*
  • Male
  • Middle Aged
  • Neoplastic Cells, Circulating / pathology
  • Pulmonary Disease, Chronic Obstructive / complications*

Grant support

The authors wish to thank the “Cancéropôle PACA” (Procan 2012–2015, Axe C) and the “Association Régionale Assistance Respiratoire à Domicile” (ARARD), Aubagne, France for their financial support. MI was supported by the “Fondation Lefort-Beaumont de l’Institut de France” through collaboration with INSERM Unit 807, Paris. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.