External quality assurance of circulating tumor cell enumeration using the CellSearch® system: A feasibility study

Jaco Kraan, Stefan Sleijfer, Michiel H. Strijbos, Michail Ignatiadis, Dieter Peeters, Jean Yves Pierga, Francoise Farace, Sabine Riethdorf, Tanja Fehm, Laura Zorzino, Arjan G J Tibbe, Marisa Maestro, Rafael Gisbert-Criado, Graeme Denton, Johann S. De Bono, Caroline Dive, John A. Foekens, Jan W. Gratama

Research output: Contribution to journalArticlepeer-review


Background: Circulating tumor cells (CTCs) are cells that have detached from solid tumors and entered the blood. CTCs can be detected, among others, by semi-automated immunomagnetic enrichment and image cytometry using CellSearch® (Veridex, Raritan, NJ). We studied the feasibility of external quality assurance (EQA) of the entire CellSearch procedure from blood draw to interpretation of results in multiple laboratories. Methods: Blood samples from six cancer patients and controls were distributed to 14 independent laboratories to test between-laboratory, between-assay, and between-instrument variation. Additionally, between-operator variability was assessed through the interpretation of blinded images of all blood samples on a website. Results: Shipment and storage of samples had no influence on CTC values. Between-instrument (coefficient of variation (CV) <12%) and between-assay variation was low (CV ≤ 20%), indicating high reproducibility. However, between-laboratory CV ranged from 45 to 64%. Although inter-operator agreement on image interpretation (Fleiss' I° statistics) ranged from " to "almost perfect," image interpretation, particularly of samples containing high numbers of apoptotic cells, was the main contributor to between-laboratory variation. Conclusions: This multicenter study shows the feasibility of an EQA program for CTC detection in patient samples, and the importance of continuation of such a program for the harmonization of CTC enumeration.

Original languageEnglish
Pages (from-to)112-118
Number of pages7
JournalCytometry Part B - Clinical Cytometry
Volume80 B
Issue number2
Publication statusPublished - Mar 2011


  • circulating tumor cells
  • external quality assessment
  • immunomagnetic enrichment
  • multicenter study
  • rare events

ASJC Scopus subject areas

  • Cell Biology
  • Histology
  • Pathology and Forensic Medicine


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