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Molecular Profiling and Prognostic Relevance of Circulating Tumor Cells in the Blood of Ovarian Cancer Patients at Primary Diagnosis and After Platinum-Based Chemotherapy
  1. Bahriye Aktas, MD,
  2. Sabine Kasimir-Bauer, PhD, Prof,
  3. Martin Heubner, MD,
  4. Rainer Kimmig, MD, Prof and
  5. Pauline Wimberger, MD, Prof
  1. Department of Gynecology and Obstetrics, University of Duisburg-Essen, Essen, Germany.
  1. Address correspondence and reprint requests to Bahriye Aktas, MD, Department of Gynecology and Obstetrics, University of Duisburg-Essen, Hufelandstrasse 55, D-45122 Essen, Germany. E-mail: bahriye.aktas{at}uk-essen.de.

Abstract

Objectives: Disseminated tumor cells (DTCs) in the bone marrow (BM) were shown to be of prognostic significance in gynecological cancers. Bone marrow aspiration is less accepted by patients compared with blood drawing. In this pilot study, we applied the AdnaTest BreastCancer based on immunomagnetic enrichment, targeting common antigens on epithelial gynecological cancers, followed by multiplex reverse transcriptase-polymerase chain reaction for selection and detection of circulating tumor cells (CTCs) in the blood of 122 ovarian cancer patients at primary diagnosis and/or after platinum-based chemotherapy. Results were compared with detection of DTC in BM.

Methods: Ten-milliliter blood was obtained before surgery (n = 86) and/or after chemotherapy (n = 70) and analyzed for CTC with the AdnaTest BreastCancer for the detection of EpCAM-, MUC-1-, and HER-2-transcripts. CA 125 was assessed in an additional single-plex reverse transcriptase-polymerase chain reaction. Bone marrow aspirates were analyzed in duplicate by immunocytochemistry using the pan-cytokeratin antibody A45-B/B3.

Results: Before surgery, CTCs were detected in 19% of patients, expressing EpCAM (31%), MUC-1 (50%), HER-2 (31%), and CA 125 (50%), respectively. After chemotherapy, the overall detection rate for CTC was 27%, thereof EpCAM (68%), MUC-1 (47%), HER2 (21%), and CA 125 (37%). The overall detection rate for DTC in the BM was 35% before surgery and 31% after therapy. A comparison between DTC and CTC resulted in a concordance rate of 59% before surgery and 56% after chemotherapy. CTC positivity significantly correlated with shorter overall survival before surgery (P = 0.0054) and after chemotherapy (P = 0.047).

Conclusions: This methodological approach might help to identify molecular targets for specific biological therapies. Blood analysis could give additional information complimentary to that obtained by DTC.

  • Circulating tumor cells
  • Disseminated tumor cells
  • Ovarian cancer
  • Platinum-based chemotherapy

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Footnotes

  • Conflict of Interest Statement: The authors declare that there are no conflicts of interest.

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