Clinical significance and molecular characteristics of circulating tumor cells and circulating tumor microemboli in patients with small-cell lung cancer

J Clin Oncol. 2012 Feb 10;30(5):525-32. doi: 10.1200/JCO.2010.33.3716. Epub 2012 Jan 17.


Purpose: Circulating tumor cells (CTCs) may have utility as surrogate biomarkers and "virtual" biopsies. We report the clinical significance and molecular characteristics of CTCs and CTC clusters, termed circulating tumor microemboli (CTM), detected in patients with small-cell lung cancer (SCLC) undergoing standard treatment.

Patients and methods: Serial blood samples from 97 patients receiving chemotherapy were analyzed using EpCam-based immunomagnetic detection and a filtration-based technique. Proliferation status (Ki67) and apoptotic morphology were examined. Associations of CTC and CTM number with clinical factors and prognosis were determined.

Results: CTCs were present in 85% of patients (77 of 97 patients) and were abundant (mean ± standard deviation = 1,589 ± 5,565). CTM and apoptotic CTCs were correlated with total CTC number and were detected in 32% and 57% of patients, respectively. Pretreatment CTCs, change in CTC number after one cycle of chemotherapy, CTM, and apoptotic CTCs were independent prognostic factors. Overall survival was 5.4 months for patients with ≥ 50 CTCs/7.5 mL of blood and 11.5 months (P < .0001) for patients with less than 50 CTCs/7.5 mL of blood before chemotherapy (hazard ratio = 2.45; 95% CI, 1.39 to 4.30; P = .002). Subpopulations of apoptotic and of proliferating solitary CTCs were detected, whereas neither were observed within cell clusters (CTM), implicating both protection from anoikis and relative resistance to cytotoxic drugs for cells within CTM.

Conclusion: Both baseline CTC number and change in CTC number after one cycle of chemotherapy are independent prognostic factors for SCLC. Molecular comparison of CTCs to cells in CTM may provide novel insights into SCLC biology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Apoptosis
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Small Cell / metabolism*
  • Carcinoma, Small Cell / pathology*
  • Cell Proliferation
  • Disease-Free Survival
  • Embolism / etiology*
  • Embolism / physiopathology
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Ki-67 Antigen / metabolism
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology*
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Myeloid Cell Leukemia Sequence 1 Protein
  • Neoplastic Cells, Circulating* / metabolism
  • Neoplastic Cells, Circulating* / pathology
  • Predictive Value of Tests
  • Proportional Hazards Models
  • Prospective Studies
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Sensitivity and Specificity


  • Biomarkers, Tumor
  • Ki-67 Antigen
  • Myeloid Cell Leukemia Sequence 1 Protein
  • Proto-Oncogene Proteins c-bcl-2