Prognostic Impact of Circulating Tumor Cell Detected Using a Novel Fluidic Cell Microarray Chip System in Patients with Breast Cancer

EBioMedicine. 2016 Sep:11:173-182. doi: 10.1016/j.ebiom.2016.07.027. Epub 2016 Jul 27.

Abstract

Various types of circulating tumor cell (CTC) detection systems have recently been developed that show a high CTC detection rate. However, it is a big challenge to find a system that can provide better prognostic value than CellSearch in head-to-head comparison. We have developed a novel semi-automated CTC enumeration system (fluidic cell microarray chip system, FCMC) that captures CTC independently of tumor-specific markers or physical properties. Here, we compared the CTC detection sensitivity and the prognostic value of FCMC with CellSearch in breast cancer patients. FCMC was validated in preclinical studies using spike-in samples and in blood samples from 20 healthy donors and 22 breast cancer patients in this study. Using spike-in samples, a statistically higher detection rate (p=0.010) of MDA-MB-231 cells and an equivalent detection rate (p=0.497) of MCF-7 cells were obtained with FCMC in comparison with CellSearch. The number of CTC detected in samples from patients that was above a threshold value as determined from healthy donors was evaluated. The CTC number detected using FCMC was significantly higher than that using CellSearch (p=0.00037). CTC numbers obtained using either FCMC or CellSearch had prognostic value, as assessed by progression free survival. The hazard ratio between CTC+ and CTC- was 4.229 in CellSearch (95% CI, 1.31 to 13.66; p=0.01591); in contrast, it was 11.31 in FCMC (95% CI, 2.245 to 57.0; p=0.000244). CTC detected using FCMC, like the CTC detected using CellSearch, have the potential to be a strong prognostic factor for cancer patients.

Keywords: Breast cancer; CellSearch; Circulating tumor cell; Fluidic cell microarray chip; Prognostic marker.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Breast Neoplasms / diagnosis*
  • Breast Neoplasms / mortality*
  • Breast Neoplasms / therapy
  • Case-Control Studies
  • Cell Count
  • Cell Line, Tumor
  • Disease Progression
  • Female
  • Humans
  • Microfluidic Analytical Techniques* / instrumentation
  • Microfluidic Analytical Techniques* / methods
  • Middle Aged
  • Neoplasm Staging
  • Neoplastic Cells, Circulating / pathology*
  • Prognosis
  • Treatment Outcome