title: A novel platform for detection of CK+ and CK- CTCs.
abstract: Metastasis is a complex, multistep process that begins with the epithelial-mesenchymal transition (EMT). Circulating tumor cells (CTC) are believed to have undergone EMT and thus lack or express low levels of epithelial markers commonly used for enrichment and/or detection of such cells. However, most current CTC detection methods target only EpCAM and/or cytokeratin (CK) to enrich epithelial CTCs, resulting in failure to recognize other, perhaps more important, CTC phenotypes that lack expression of these markers. Here, we describe a population of complex aneuploid CTCs that do not express CK or CD45 antigen in patients with breast, ovarian, or colorectal cancer. These cells were not observed in healthy subjects. We show that the primary epithelial tumors were characterized by similar complex aneuploidy, indicating conversion to an EMT phenotype in the captured cells. Collectively, our study provides a new method for highly efficient capture of previously unrecognized populations of CTCs.
  
  
  CONCLUSIONS
  Current assays for CTC capture likely miss populations of cells that have undergone EMT. Capture and study of CTCs that have undergone EMT would allow a better understanding of the mechanisms driving metastasis.
authors.affiliation: Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Chad V
authors.initials: CV
authors.lastname: Pecot
authors.forename: Farideh Z
authors.initials: FZ
authors.lastname: Bischoff
authors.forename: Julie Ann
authors.initials: JA
authors.lastname: Mayer
authors.forename: Karina L
authors.initials: KL
authors.lastname: Wong
authors.forename: Tam
authors.initials: T
authors.lastname: Pham
authors.forename: Justin
authors.initials: J
authors.lastname: Bottsford-Miller
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Stone
authors.forename: Yvonne G
authors.initials: YG
authors.lastname: Lin
authors.forename: Padmavathi
authors.initials: P
authors.lastname: Jaladurgam
authors.forename: Ju Won
authors.initials: JW
authors.lastname: Roh
authors.forename: Blake W
authors.initials: BW
authors.lastname: Goodman
authors.forename: William M
authors.initials: WM
authors.lastname: Merritt
authors.forename: Tony J
authors.initials: TJ
authors.lastname: Pircher
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Mikolajczyk
authors.forename: Alpa M
authors.initials: AM
authors.lastname: Nick
authors.forename: Joseph
authors.initials: J
authors.lastname: Celestino
authors.forename: Cathy
authors.initials: C
authors.lastname: Eng
authors.forename: Lee M
authors.initials: LM
authors.lastname: Ellis
authors.forename: Michael T
authors.initials: MT
authors.lastname: Deavers
authors.forename: Anil K
authors.initials: AK
authors.lastname: Sood
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood; D001943:Breast Neoplasms / Q000097:blood / Q000235:genetics / Q000473:pathology*; D015179:Colorectal Neoplasms / Q000097:blood / Q000235:genetics / Q000473:pathology*; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D005260:Female; D006801:Humans; D007633:Keratins / Q000032:analysis / Q000097:blood* / Q000235:genetics; D009362:Neoplasm Metastasis; D009360:Neoplastic Cells, Circulating / Q000737:chemistry* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000097:blood / Q000235:genetics / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; D007633:Keratins