title: Molecular characterization of circulating tumor cells in patients with ovarian cancer improves their prognostic significance -- a study of the OVCAD consortium.
abstract: OBJECTIVE
  The study aims at identifying novel markers for circulating tumor cells (CTCs) in patients with epithelial ovarian cancer (EOC), and at evaluating their impact on outcome.
  
  
  METHODS
  Microarray analysis comparing matched EOC tissues and peripheral blood leucocytes (N=35) was performed to identify novel CTC markers. Gene expression of these novel markers and of EpCAM was analyzed using RT-qPCR in blood samples taken from healthy females (N=39) and from EOC patients (N=216) before primary treatment and six months after adjuvant chemotherapy. All samples were enriched by density gradient centrifugation. CTC positivity was defined by over-expression of at least one gene as compared to the healthy control group.
  
  
  RESULTS
  CTC were detected in 24.5% of the baseline and 20.4% of the follow-up samples, of which two thirds were identified by overexpression of the cyclophilin C gene (PPIC), and just a few by EpCAM overexpression. The presence of CTCs at baseline correlated with the presence of ascites, sub-optimal debulking, and elevated CA-125 and HE-4 levels, whereas CTC during follow-up occurred more often in older and platinum resistant patients. PPIC positive CTCs during follow-up were significantly more often detected in the platinum resistant than in the platinum sensitive patient group, and indicated poor outcome independent from classical prognostic parameters.
  
  
  CONCLUSIONS
  Molecular characterization of CTC is superior to a mere CTC enumeration or even be the rationale for CTC diagnostics at all. Ultimately CTC diagnostics may lead to more personalized treatment of EOC, especially in the recurrent situation.
authors.affiliation: Department of Obstetrics and Gynecology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria; Ludwig Boltzmann Gesellschaft, Cluster Translational Oncology, Waehringer Guertel 18-20, 1090 Vienna, Austria. Electronic address: eva.obermayr@meduniwien.ac.at.
authors.forename: Eva
authors.initials: E
authors.lastname: Obermayr
authors.affiliation: Department of Obstetrics and Gynecology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.
authors.forename: Dan Cacsire
authors.initials: DC
authors.lastname: Castillo-Tong
authors.affiliation: Department of Obstetrics and Gynecology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.
authors.forename: Dietmar
authors.initials: D
authors.lastname: Pils
authors.affiliation: Department of Obstetrics and Gynecology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.
authors.forename: Paul
authors.initials: P
authors.lastname: Speiser
authors.affiliation: Department of Gynecology, European Competence Center for Ovarian Cancer; Campus Virchow Klinikum, Charité, Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany.
authors.forename: Ioana
authors.initials: I
authors.lastname: Braicu
authors.affiliation: Division of Gynecological Oncology, Department of Obstetrics and Gynecology, Universitaire Ziekenhuizen Leuven, Katholieke Universiteit Leuven, Herestraat 49, 3000 Leuven, Belgium.
authors.forename: Toon
authors.initials: T
authors.lastname: Van Gorp
authors.affiliation: Department of Gynecology and Gynecologic Oncology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Mahner
authors.affiliation: Department of Gynecology, European Competence Center for Ovarian Cancer; Campus Virchow Klinikum, Charité, Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany.
authors.forename: Jalid
authors.initials: J
authors.lastname: Sehouli
authors.affiliation: Division of Gynecological Oncology, Department of Obstetrics and Gynecology, Universitaire Ziekenhuizen Leuven, Katholieke Universiteit Leuven, Herestraat 49, 3000 Leuven, Belgium.
authors.forename: Ignace
authors.initials: I
authors.lastname: Vergote
authors.affiliation: Department of Obstetrics and Gynecology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria; Ludwig Boltzmann Gesellschaft, Cluster Translational Oncology, Waehringer Guertel 18-20, 1090 Vienna, Austria.
authors.forename: Robert
authors.initials: R
authors.lastname: Zeillinger
mesh_terms: D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000235:genetics; D018394:CA-125 Antigen / Q000097:blood; D000077216:Carcinoma, Ovarian Epithelial; D015815:Cell Adhesion Molecules / Q000235:genetics; D000072622:Cyclophilin C; D021983:Cyclophilins / Q000235:genetics; D000071858:Epithelial Cell Adhesion Molecule; D005260:Female; D006801:Humans; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology*; D009360:Neoplastic Cells, Circulating / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology*; D011379:Prognosis; D011506:Proteins / Q000032:analysis; D000081102:WAP Four-Disulfide Core Domain Protein 2
chemical_list: D000951:Antigens, Neoplasm; D018394:CA-125 Antigen; D015815:Cell Adhesion Molecules; C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule; D011506:Proteins; D000081102:WAP Four-Disulfide Core Domain Protein 2; C569698:WFDC2 protein, human; D021983:Cyclophilins; D000072622:Cyclophilin C