Molecular characterization of circulating tumor cells in patients with ovarian cancer improves their prognostic significance -- a study of the OVCAD consortium

Gynecol Oncol. 2013 Jan;128(1):15-21. doi: 10.1016/j.ygyno.2012.09.021. Epub 2012 Sep 24.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antigens, Neoplasm / genetics
  • CA-125 Antigen / blood
  • Carcinoma, Ovarian Epithelial
  • Cell Adhesion Molecules / genetics
  • Cyclophilin C
  • Cyclophilins / genetics
  • Epithelial Cell Adhesion Molecule
  • Female
  • Humans
  • Middle Aged
  • Neoplasms, Glandular and Epithelial / diagnosis*
  • Neoplasms, Glandular and Epithelial / mortality
  • Neoplasms, Glandular and Epithelial / pathology*
  • Neoplastic Cells, Circulating / metabolism*
  • Ovarian Neoplasms / diagnosis*
  • Ovarian Neoplasms / mortality
  • Ovarian Neoplasms / pathology*
  • Prognosis
  • Proteins / analysis
  • WAP Four-Disulfide Core Domain Protein 2


  • Antigens, Neoplasm
  • CA-125 Antigen
  • Cell Adhesion Molecules
  • EPCAM protein, human
  • Epithelial Cell Adhesion Molecule
  • Proteins
  • WAP Four-Disulfide Core Domain Protein 2
  • WFDC2 protein, human
  • Cyclophilins
  • Cyclophilin C