title: The Use of a New CellCollector to Isolate Circulating Tumor Cells from the Blood of Patients with Different Stages of Prostate Cancer and Clinical Outcomes - A Proof-of-Concept Study.
abstract: METHODS
  Circulating tumor cells (CTCs) constitute a useful approach for personalized medicine. Nevertheless, the isolation of these cells remains very challenging because they rarely circulate in the blood. Another current problem is the cancer-specific characterization of these cells, which requires a method that allows for the molecular and immunocytochemical profiling of all captured cells. The purpose of our proof of concept study was to investigate the use of a medical wire (CellCollector, GILUPI) to isolate CTCs in the blood of prostate cancer (PCa) patients, which allowed CTCs to be counted and molecularly characterized. Forty-three PCa patients in different stages and 11 control subjects were studied. Some randomized samples were used to detect tumor-associated transcripts, such as prostate-specific membrane antigen (PSMA), prostate-specific antigen (PSA) and epidermal growth factor receptor (EGFR), in the isolated CTCs.
  
  
  RESULTS
  The mean CTC counts were 4.6 CTCs [range, 0-8] in patients with localized PCa, 16.8 CTCs [range, 10-25] in patients with locally advanced PCa, and 26.8 CTCs [range, 0-98] in patients with metastatic PCa. The median follow-up time was 24 months, and there was a significant difference in the cancer-specific survival rates. Patients with CTC counts under 5 CTCs lived significantly longer (p = 0.035) than patients with more than 5 CTCs. We also demonstrated that the captured CTCs could be molecularly characterized. We detected tumor-associated transcripts of EGFR and PSMA in patients with metastatic PCa in 42.8% and 14.3% of the analyzed samples, respectively.
  
  
  CONCLUSIONS
  Our results indicate that the sensitive isolation and molecular characterization of CTCs can be achieved ex vivo using the wire. Patients with more than 5 CTCs had a mortality risk that was 7.0 times greater that of those with fewer than 5 CTCs (hazard ratio 7.0 95%, CI 1.1-29.39). This proof of concept was required for the approval of the use of the CellCollector in a clinical study for the in vivo isolation of CTCs from the blood stream of PCa patients by the Federal Institute for Drugs and Medical devices (Germany, BfArM).
authors.affiliation: Martin Luther University Halle-Wittenberg, Clinic of Urology and Transplantation, Ernst-Grube-Str.40, 06120, Halle/Saale, Germany.
authors.forename: Gerit
authors.initials: G
authors.lastname: Theil
authors.affiliation: Martin Luther University Halle-Wittenberg, Clinic of Urology and Transplantation, Ernst-Grube-Str.40, 06120, Halle/Saale, Germany.
authors.forename: Kersten
authors.initials: K
authors.lastname: Fischer
authors.affiliation: GILUPI-GmbH, Potsdam, Mühlenberg 11, Germany.
authors.forename: Ekkehard
authors.initials: E
authors.lastname: Weber
authors.affiliation: Martin Luther University Halle-Wittenberg, Institute of Physiological Chemistry, Hollystr. 1, 06120, Halle/Saale, Germany.
authors.forename: Rita
authors.initials: R
authors.lastname: Medek
authors.affiliation: Martin Luther University Halle-Wittenberg, Clinic of Urology and Transplantation, Ernst-Grube-Str.40, 06120, Halle/Saale, Germany.
authors.forename: Raschid
authors.initials: R
authors.lastname: Hoda
authors.affiliation: GILUPI-GmbH, Potsdam, Mühlenberg 11, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Lücke
authors.affiliation: Martin Luther University Halle-Wittenberg, Clinic of Urology and Transplantation, Ernst-Grube-Str.40, 06120, Halle/Saale, Germany.
authors.forename: Paolo
authors.initials: P
authors.lastname: Fornara
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D002452:Cell Count; D045744:Cell Line, Tumor; D002469:Cell Separation / Q000379:methods*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D046210:Microfluidic Analytical Techniques; D008875:Middle Aged; D008954:Models, Biological; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D009360:Neoplastic Cells, Circulating / Q000378:metabolism; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D015996:Survival Rate
chemical_list: D017430:Prostate-Specific Antigen