title: Phenotypic diversity of circulating tumour cells in patients with metastatic castration-resistant prostate cancer.
abstract: To use a non-biased assay for circulating tumour cells (CTCs) in patients with prostate cancer (PCa) in order to identify non-traditional CTC phenotypes potentially excluded by conventional detection methods that are reliant on antigen- and/or size-based enrichment.
  
  
  
  A total of 41 patients with metastatic castration-resistant PCa (mCRPC) and 20 healthy volunteers were analysed on the Epic CTC platform, via high-throughput imaging of DAPI expression and CD45/cytokeratin (CK) immunofluorescence (IF) on all circulating nucleated cells plated on glass slides. To confirm the PCa origin of CTCs, IF was used for androgen receptor (AR) expression and fluorescence in situ hybridization was used for PTEN and ERG assessment.
  
  
  
  Traditional CTCs (CD45-/CK+/morphologically distinct) were identified in all patients with mCRPC and we also identified CTC clusters and non-traditional CTCs in patients with mCRPC, including CK-and apoptotic CTCs. Small CTCs (≤white blood cell size) were identified in 98% of patients with mCRPC. Total, traditional and non-traditional CTCs were significantly increased in patients who were deceased vs alive after 18 months; however, only non-traditional CTCs were associated with overall survival. Traditional and total CTC counts according to the Epic platform in the mCRPC cohort were also significantly correlated with CTC counts according to the CellSearch system.
  
  
  
  Heterogeneous non-traditional CTC populations are frequent in mCRPC and may provide additional prognostic or predictive information.
authors.affiliation: Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA.
authors.forename: Andrew S
authors.initials: AS
authors.lastname: McDaniel
authors.affiliation: The Institute of Cancer Research, London, UK.|Royal Marsden NHS Foundation Trust, London, UK.
authors.forename: Roberta
authors.initials: R
authors.lastname: Ferraldeschi
authors.affiliation: Epic Sciences, San Diego, CA, USA.
authors.forename: Rachel
authors.initials: R
authors.lastname: Krupa
authors.affiliation: Epic Sciences, San Diego, CA, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Landers
authors.affiliation: Epic Sciences, San Diego, CA, USA.
authors.forename: Ryon
authors.initials: R
authors.lastname: Graf
authors.affiliation: Epic Sciences, San Diego, CA, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Louw
authors.affiliation: Epic Sciences, San Diego, CA, USA.
authors.forename: Adam
authors.initials: A
authors.lastname: Jendrisak
authors.affiliation: Epic Sciences, San Diego, CA, USA.
authors.forename: Natalee
authors.initials: N
authors.lastname: Bales
authors.affiliation: Epic Sciences, San Diego, CA, USA.
authors.forename: Dena
authors.initials: D
authors.lastname: Marrinucci
authors.affiliation: The Institute of Cancer Research, London, UK.|Royal Marsden NHS Foundation Trust, London, UK.
authors.forename: Zafeiris
authors.initials: Z
authors.lastname: Zafeiriou
authors.affiliation: The Institute of Cancer Research, London, UK.
authors.forename: Penelope
authors.initials: P
authors.lastname: Flohr
authors.affiliation: The Institute of Cancer Research, London, UK.|Royal Marsden NHS Foundation Trust, London, UK.
authors.forename: Spyridon
authors.initials: S
authors.lastname: Sideris
authors.affiliation: The Institute of Cancer Research, London, UK.
authors.forename: Mateus
authors.initials: M
authors.lastname: Crespo
authors.affiliation: The Institute of Cancer Research, London, UK.
authors.forename: Ines
authors.initials: I
authors.lastname: Figueiredo
authors.affiliation: The Institute of Cancer Research, London, UK.|Royal Marsden NHS Foundation Trust, London, UK.
authors.forename: Joaquin
authors.initials: J
authors.lastname: Mateo
authors.affiliation: The Institute of Cancer Research, London, UK.|Royal Marsden NHS Foundation Trust, London, UK.
authors.forename: Johann S
authors.initials: JS
authors.lastname: de Bono
authors.affiliation: Epic Sciences, San Diego, CA, USA.
authors.forename: Ryan
authors.initials: R
authors.lastname: Dittamore
authors.affiliation: Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA.|Department Urology, University of Michigan Medical School, Ann Arbor, MI, USA.|Comprehensive Cancer Center, Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, MI, USA.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Tomlins
authors.affiliation: The Institute of Cancer Research, London, UK.|Royal Marsden NHS Foundation Trust, London, UK.
authors.forename: Gerhardt
authors.initials: G
authors.lastname: Attard
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood; D018450:Disease Progression; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000235:genetics / Q000473:pathology*; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D051059:PTEN Phosphohydrolase / Q000097:blood / Q000235:genetics; D010641:Phenotype; D017430:Prostate-Specific Antigen / Q000097:blood / Q000235:genetics; D064129:Prostatic Neoplasms, Castration-Resistant / Q000097:blood* / Q000235:genetics / Q000473:pathology*; D011944:Receptors, Androgen / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D011944:Receptors, Androgen; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D017430:Prostate-Specific Antigen
keywords: 
  ERG
  ; 
  PTEN
  ; circulating tumour cells; liquid biopsy; metastatic castration-resistant prostate cancer