title: Microfluidic enrichment of circulating tumor cells in patients with clinically localized prostate cancer.
abstract: Circulating tumor cells (CTC) have become an important tool in the monitoring of patients with advanced prostate cancer (PC). The role of CTC in localized disease has been addressed by only few studies. However, results of CTC analyses are strongly dependent on the platform used for CTC enrichment and detection. In the present study, a microfluidic platform allowing for antigen-independent enrichment of CTC was investigated for its ability to detect CTC in patients with clinically localized PC.
  
  
  
  Blood (2ml) was collected preoperatively from 50 consecutive patients undergoing radical prostatectomy for clinically localized PC. CTC were enriched using a microfluidic ratchet mechanism allowing separation of CTC from white blood cells based on differences in size and deformability. Enriched cells were stained for immunofluorescence with antibodies targeting pancytokeratin, epithelial cell adhesion molecule, and CD45. In 21 patients, we performed staining for the androgen receptor. CTC counts were correlated with clinical and pathological parameters using the Wilcoxon-Mann-Whitney test for continuous parameters and Chi-square test for categorical parameters.
  
  
  
  CTC were detected in 25 (50%) patients. The median number of CTC in CTC-positive patients was 9 CTC/2ml (range: 1-417). Pancytokeratin positive CTC showed expression of androgen the receptor. We observed no correlation between CTC counts and prostate-specific antigen concentration, tumor stage, lymph node stage, or Gleason grade.
  
  
  
  In a representative cohort of patients with clinically localized PC, CTC can be detected in a considerable proportion of patients when using a new microfluidic ratchet mechanism. This encourages further studies assessing the prognostic effect of antigen-independent enriched CTC in patients with PC.
authors.affiliation: Vancouver Prostate Centre, University of British Columbia, Vancouver, Canada; Department of Urology, University Hospital, Tübingen, Germany.
authors.forename: Tilman
authors.initials: T
authors.lastname: Todenhöfer
authors.affiliation: Vancouver Prostate Centre, University of British Columbia, Vancouver, Canada; Department of Mechanical Engineering, University of British Columbia, Vancouver, Canada.
authors.forename: Emily Sunyong
authors.initials: ES
authors.lastname: Park
authors.affiliation: Vancouver Prostate Centre, University of British Columbia, Vancouver, Canada; Department of Mechanical Engineering, University of British Columbia, Vancouver, Canada.
authors.forename: Simon
authors.initials: S
authors.lastname: Duffy
authors.affiliation: Vancouver Prostate Centre, University of British Columbia, Vancouver, Canada; Department of Mechanical Engineering, University of British Columbia, Vancouver, Canada.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Deng
authors.affiliation: Vancouver Prostate Centre, University of British Columbia, Vancouver, Canada; Department of Mechanical Engineering, University of British Columbia, Vancouver, Canada.
authors.forename: Chao
authors.initials: C
authors.lastname: Jin
authors.affiliation: Vancouver Prostate Centre, University of British Columbia, Vancouver, Canada.
authors.forename: Hamidreza
authors.initials: H
authors.lastname: Abdi
authors.affiliation: Vancouver Prostate Centre, University of British Columbia, Vancouver, Canada; Department of Mechanical Engineering, University of British Columbia, Vancouver, Canada.
authors.forename: Hongshen
authors.initials: H
authors.lastname: Ma
authors.affiliation: Vancouver Prostate Centre, University of British Columbia, Vancouver, Canada. Electronic address: pblack@mail.ubc.ca.
authors.forename: Peter C
authors.initials: PC
authors.lastname: Black
mesh_terms: D000230:Adenocarcinoma / Q000097:blood* / Q000473:pathology / Q000601:surgery; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D002452:Cell Count; D002469:Cell Separation / Q000295:instrumentation / Q000379:methods*; D048430:Cell Shape; D000071858:Epithelial Cell Adhesion Molecule / Q000097:blood; D004867:Equipment Design; D006801:Humans; D007633:Keratins / Q000097:blood; D056656:Lab-On-A-Chip Devices; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000097:blood; D009360:Neoplastic Cells, Circulating; D015588:Observer Variation; D011300:Preoperative Care; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000097:blood* / Q000473:pathology / Q000601:surgery; D011944:Receptors, Androgen / Q000097:blood
chemical_list: C410798:AR protein, human; D014408:Biomarkers, Tumor; C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule; D009363:Neoplasm Proteins; D011944:Receptors, Androgen; D007633:Keratins
keywords: Biomarker; Blood; Circulating tumor cells; Minimal residual disease; Prostate cancer; Prostatectomy