title: External quality assurance of circulating tumor cell enumeration using the CellSearch(®) system: a feasibility study.
abstract: 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' κ statistics) ranged from "substantial" 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.
authors.affiliation: Department of Medical Oncology, Erasmus Medical Center, Rotterdam, The Netherlands. j.kraan@erasmusmc.nl
authors.forename: Jaco
authors.initials: J
authors.lastname: Kraan
authors.forename: Stefan
authors.initials: S
authors.lastname: Sleijfer
authors.forename: Michiel H
authors.initials: MH
authors.lastname: Strijbos
authors.forename: Michail
authors.initials: M
authors.lastname: Ignatiadis
authors.forename: Dieter
authors.initials: D
authors.lastname: Peeters
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Pierga
authors.forename: Francoise
authors.initials: F
authors.lastname: Farace
authors.forename: Sabine
authors.initials: S
authors.lastname: Riethdorf
authors.forename: Tanja
authors.initials: T
authors.lastname: Fehm
authors.forename: Laura
authors.initials: L
authors.lastname: Zorzino
authors.forename: Arjan G J
authors.initials: AG
authors.lastname: Tibbe
authors.forename: Marisa
authors.initials: M
authors.lastname: Maestro
authors.forename: Rafael
authors.initials: R
authors.lastname: Gisbert-Criado
authors.forename: Graeme
authors.initials: G
authors.lastname: Denton
authors.forename: Johann S
authors.initials: JS
authors.lastname: de Bono
authors.forename: Caroline
authors.initials: C
authors.lastname: Dive
authors.forename: John A
authors.initials: JA
authors.lastname: Foekens
authors.forename: Jan W
authors.initials: JW
authors.lastname: Gratama
mesh_terms: D002452:Cell Count; D005240:Feasibility Studies; D005434:Flow Cytometry / Q000592:standards*; D006801:Humans; D009369:Neoplasms / Q000097:blood / Q000473:pathology*; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D011786:Quality Control; D015203:Reproducibility of Results