Eva Obermayr1, Dan Cacsire Castillo-Tong2, Dietmar Pils2, Paul Speiser2, Ioana Braicu3, Toon Van Gorp4, Sven Mahner5, Jalid Sehouli3, Ignace Vergote4, Robert Zeillinger6. 1. 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. 2. Department of Obstetrics and Gynecology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria. 3. Department of Gynecology, European Competence Center for Ovarian Cancer; Campus Virchow Klinikum, Charité, Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany. 4. Division of Gynecological Oncology, Department of Obstetrics and Gynecology, Universitaire Ziekenhuizen Leuven, Katholieke Universiteit Leuven, Herestraat 49, 3000 Leuven, Belgium. 5. Department of Gynecology and Gynecologic Oncology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany. 6. 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.
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.
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: Myoung-Hwan Park; Eduardo Reátegui; Wei Li; Shannon N Tessier; Keith H K Wong; Anne E Jensen; Vishal Thapar; David Ting; Mehmet Toner; Shannon L Stott; Paula T Hammond Journal: J Am Chem Soc Date: 2017-02-09 Impact factor: 15.419
Authors: Scott M Langevin; E Andres Houseman; William P Accomando; Devin C Koestler; Brock C Christensen; Heather H Nelson; Margaret R Karagas; Carmen J Marsit; John K Wiencke; Karl T Kelsey Journal: Epigenetics Date: 2014-03-26 Impact factor: 4.528
Authors: Cesar M Castro; Hyungsoon Im; Christine Le; Hakho Lee; Ralph Weissleder; Michael J Birrer Journal: Cancer Metastasis Rev Date: 2015-03 Impact factor: 9.264
Authors: Vanessa M Peterson; Cesar M Castro; Jaehoon Chung; Nathan C Miller; Adeeti V Ullal; Maria D Castano; Richard T Penson; Hakho Lee; Michael J Birrer; Ralph Weissleder Journal: Proc Natl Acad Sci U S A Date: 2013-12-02 Impact factor: 11.205