Prognostic value of circulating endothelial cells in metastatic colorectal cancer

Oncotarget. 2017 Jun 6;8(23):37491-37501. doi: 10.18632/oncotarget.16397.


Background: There is urgent need for improved staging in patients with metastatic colorectal cancer (mCRC). In this study, we evaluated the prognostic value of circulating endothelial cells (CEC) in comparison with circulating tumor cells (CTC) in patients with mCRC amenable for potentially curative surgery.

Methods: A total of 140 patients were enrolled prospectively. CTC and CEC were measured with the CellSearch System (Veridex, NJ, USA). Cut-off values were determined using ROC analyses. Prognostic factors were identified by Cox proportional hazards models.

Results: ROC analyses revealed ≥ 21 CEC as cut-off levels for detection, which was present in 68 (49%). CEC detection was associated with female gender (p = 0.03) only, whereas CTC detection was associated with presence of the primary tumor (p = 0.007), metastasis size (p < 0.001), bilobar liver metastases (p = 0.02), CEA (p < 0.001) and CA 19-9 levels (p < 0.001). On multivariate analysis only CEC detection (HR 1.81; p = 0.03) and preoperative CA19-9 levels (HR 2.28, p = 0.005) were revealed as independent predictors of poor survival.

Conclusions: CEC are of stronger prognostic value than CTC. Further studies are required to validate these results and to evaluate CEC as predictive biomarker for systemic therapy alone as well as in combination with other markers such as CA19-9.

Keywords: CEC; CTC; circulating endothelial cells; circulating tumor cells; colorectal cancer.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / blood
  • Colorectal Neoplasms / blood
  • Colorectal Neoplasms / drug therapy
  • Colorectal Neoplasms / pathology*
  • Endothelial Cells / pathology*
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Liver Neoplasms / blood
  • Liver Neoplasms / drug therapy
  • Liver Neoplasms / secondary*
  • Male
  • Middle Aged
  • Neoplastic Cells, Circulating / pathology*
  • Outcome Assessment, Health Care / methods
  • Outcome Assessment, Health Care / statistics & numerical data
  • Prognosis
  • Proportional Hazards Models
  • Prospective Studies


  • Biomarkers, Tumor