Predictive value of circulating tumor cells (CTCs) captured by microfluidic device in patients with epithelial ovarian cancer

Gynecol Oncol. 2017 May;145(2):361-365. doi: 10.1016/j.ygyno.2017.02.042. Epub 2017 Mar 6.

Abstract

Objective: To test an electrically conductive chip, incorporating a nanoroughened microfluidic platform for the capture of circulating tumor cells (CTCs), and assess its clinical merit in instances of epithelial ovarian cancer (EOC).

Methods: A total of 54 patients with EOC recruited between August 2014 and May 2015 were enrolled in this prospective study. CTCs in peripheral blood were detected in advance of primary tumor resection and before initiating adjuvant chemotherapy for recurrent disease. We identified CTCs as EpCAM-positive and DAPI-positive, and CD45-negative feature.

Results: Twenty-four patients with primary disease and 30 patients with recurrences were included in the study. CTCs were detected in 98.1% (53/54). In newly diagnosed patients, median counts of single CTCs and CTC clusters were 4 (0-13) and 1(0-14), respectively. In those with recurrences, median counts were 3 (1-9) and 1(0-24), respectively. Such counts did not differ significantly by tumor stage or by serum CA125 level; but progression-free survival declined at a cutpoint of ≥3 CTCs, and CTC-cluster positivity correlated with platinum resistance. Isolated CTCs (successfully cultured ex vivo in two patients) showed greater sensitivity to anticancer drugs and proliferated more rapidly than did established cell lines.

Conclusion: Proof-of-concept was provided for an electrically conductive and nanoroughened microfluidic platform-based chip designed to capture CTCs in patients with EOC. A larger patient sampling and longer duration of follow-up are needed to determine its suitability for clinical use.

Keywords: Capture; Circulating tumor cells; Clusters; Electrochemical immunosensor; Isolation; Ovarian cancer.

MeSH terms

  • Carcinoma, Ovarian Epithelial
  • Cell Line, Tumor
  • Female
  • Humans
  • Lab-On-A-Chip Devices
  • Microfluidic Analytical Techniques / instrumentation
  • Microfluidic Analytical Techniques / methods
  • Middle Aged
  • Neoplasm Recurrence, Local / blood
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Staging
  • Neoplasms, Glandular and Epithelial / blood*
  • Neoplasms, Glandular and Epithelial / pathology*
  • Neoplastic Cells, Circulating / pathology*
  • Ovarian Neoplasms / blood*
  • Ovarian Neoplasms / pathology*