title: Tumor cells circulate in the peripheral blood of all major carcinomas but not in healthy subjects or patients with nonmalignant diseases.
abstract: OBJECTIVE
  The purpose of this study was to determine the accuracy, precision, and linearity of the CellSearch system and evaluate the number of circulating tumor cells (CTCs) per 7.5 mL of blood in healthy subjects, patients with nonmalignant diseases, and patients with a variety of metastatic carcinomas.
  
  
  METHODS
  The CellSearch system was used to enumerate CTCs in 7.5 mL of blood. Blood samples spiked with cells from tumor cell lines were used to establish analytical accuracy, reproducibility, and linearity. Prevalence of CTCs was determined in blood from 199 patients with nonmalignant diseases, 964 patients with metastatic carcinomas, and 145 healthy donors.
  
  
  RESULTS
  Enumeration of spiked tumor cells was linear over the range of 5 to 1,142 cells, with an average recovery of >/=85% at each spike level. Only 1 of the 344 (0.3%) healthy and nonmalignant disease subjects had >/=2 CTCs per 7.5 mL of blood. In 2,183 blood samples from 964 metastatic carcinoma patients, CTCs ranged from 0 to 23,618 CTCs per 7.5 mL (mean, 60 +/- 693 CTCs per 7.5 mL), and 36% (781 of 2,183) of the specimens had >/=2 CTCs. Detection of >/=2 CTCs occurred at the following rates: 57% (107 of 188) of prostate cancers, 37% (489 of 1,316) of breast cancers, 37% (20 of 53) of ovarian cancers, 30% (99 of 333) of colorectal cancers, 20% (34 of 168) of lung cancers, and 26% (32 of 125) of other cancers.
  
  
  CONCLUSIONS
  The CellSearch system can be standardized across multiple laboratories and may be used to determine the clinical utility of CTCs. CTCs are extremely rare in healthy subjects and patients with nonmalignant diseases but present in various metastatic carcinomas with a wide range of frequencies.
authors.affiliation: Immunicon Corporation, Huntingdon Valley, Pennsylvania 19006, USA. jallard@immunicon.com
authors.forename: W Jeffrey
authors.initials: WJ
authors.lastname: Allard
authors.forename: Jeri
authors.initials: J
authors.lastname: Matera
authors.forename: M Craig
authors.initials: MC
authors.lastname: Miller
authors.forename: Madeline
authors.initials: M
authors.lastname: Repollet
authors.forename: Mark C
authors.initials: MC
authors.lastname: Connelly
authors.forename: Chandra
authors.initials: C
authors.lastname: Rao
authors.forename: Arjan G J
authors.initials: AG
authors.lastname: Tibbe
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Uhr
authors.forename: Leon W M M
authors.initials: LW
authors.lastname: Terstappen
mesh_terms: D000328:Adult; D001331:Automation; D001681:Biological Assay; D002277:Carcinoma / Q000473:pathology*; D016022:Case-Control Studies; D003584:Cytological Techniques; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009360:Neoplastic Cells, Circulating; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity