Oncotarget

Research Papers:

EpCAMhigh and EpCAMlow circulating tumor cells in metastatic prostate and breast cancer patients

Sanne de Wit, Mariangela Manicone, Elisabetta Rossi, Rita Lampignano, Liwen Yang, Beate Zill, Alvera Rengel-Puertas, Marianne Ouhlen, Mateus Crespo, Anne Margreet Sofie Berghuis, Kiki Carlijn Andree, Riccardo Vidotto, Elisabeth Katharina Trapp, Marie Tzschaschel, Emeline Colomba, Gemma Fowler, Penelope Flohr, Pasquale Rescigno, Mariane Sousa Fontes, Rita Zamarchi, Tanja Fehm, Hans Neubauer, Brigitte Rack, Marianna Alunni-Fabbroni, Françoise Farace, Johann De Bono, Maarten Joost IJzerman and Leonardus Wendelinus Mathias Marie Terstappen _

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Oncotarget. 2018; 9:35705-35716. https://doi.org/10.18632/oncotarget.26298

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Abstract

Sanne de Wit1, Mariangela Manicone2, Elisabetta Rossi2,3, Rita Lampignano4, Liwen Yang4, Beate Zill5, Alvera Rengel-Puertas5, Marianne Ouhlen6,7, Mateus Crespo8, Anne Margreet Sofie Berghuis9, Kiki Carlijn Andree1, Riccardo Vidotto2, Elisabeth Katharina Trapp5, Marie Tzschaschel10, Emeline Colomba11, Gemma Fowler8, Penelope Flohr8, Pasquale Rescigno8,12, Mariane Sousa Fontes8,12, Rita Zamarchi2, Tanja Fehm4, Hans Neubauer4, Brigitte Rack5, Marianna Alunni-Fabbroni5, Françoise Farace6,7, Johann De Bono8,12, Maarten Joost IJzerman9 and Leonardus Wendelinus Mathias Marie Terstappen1

1Department of Medical Cell BioPhysics, Faculty of Sciences and Technology, MIRA Institute, University of Twente, Enschede, The Netherlands

2Veneto Institute of Oncology IOV–IRCCS, Padova, Italy

3DiSCOG–University of Padova, Padova, Italy

4Department of Obstetrics and Gynecology, Heinrich-Heine-University, Düsseldorf, Germany

5Department of Gynecology and Obstetrics, Ludwig-Maximilians-University, Munich, Germany

6“Circulating Tumor Cells” Translational Platform, Gustave Roussy, Université Paris-Saclay, Villejuif, France

7“Identification of Molecular Predictors and New Targets for Cancer Treatment”, Gustave Roussy, Université Paris-Saclay, Villejuif, France

8Cancer Biomarkers, The Institute of Cancer Research, Sutton, United Kingdom

9Department of Health Technology and Services Research, Faculty of Behavioural, Management and Social Sciences, MIRA Institute, University of Twente, Enschede, The Netherlands

10Department of Gynecology and Obstetrics, Ulm-University, Munich, Germany

11Department of Medicine, Gustave Roussy, Université Paris-Saclay, Villejuif, France

12Prostate Cancer Targeted Therapy Group, The Royal Marsden NHS Foundation Trust, The Institute of Cancer Research, Sutton, United Kingdom

Correspondence to:

Leonardus Wendelinus Mathias Marie Terstappen, email: l.w.m.m.terstappen@utwente.nl

Keywords: circulating tumor cells (CTC); EpCAM; castrate-resistant prostate cancer (CRPC); metastatic breast cancer (mBC); epithelial-to-mesenchymal transition (EMT)

Received: August 10, 2018     Accepted: October 25, 2018     Published: November 02, 2018

ABSTRACT

The presence of high expressing epithelial cell adhesion molecule (EpCAMhigh) circulating tumor cells (CTC) enumerated by CellSearch® in blood of cancer patients is strongly associated with poor prognosis. This raises the question about the presence and relation with clinical outcome of low EpCAM expressing CTC (EpCAMlow CTC). In the EU-FP7 CTC-Trap program, we investigated the presence of EpCAMhigh and EpCAMlow CTC using CellSearch, followed by microfiltration of the EpCAMhigh CTC depleted blood. Blood samples of 108 castration-resistant prostate cancer patients and 22 metastatic breast cancer patients were processed at six participating sites, using protocols and tools developed in the CTC-Trap program. Of the prostate cancer patients, 53% had ≥5 EpCAMhigh CTC and 28% had ≥5 EpCAMlow CTC. For breast cancer patients, 32% had ≥5 EpCAMhigh CTC and 36% had ≥5 EpCAMlow CTC. 70% of prostate cancer patients and 64% of breast cancer patients had in total ≥5 EpCAMhigh and/or EpCAMlow CTC, increasing the number of patients in whom CTC are detected. Castration-resistant prostate cancer patients with ≥5 EpCAMhigh CTC had shorter overall survival versus those with <5 EpCAMhigh CTC (p = 0.000). However, presence of EpCAMlow CTC had no relation with overall survival. This emphasizes the importance to demonstrate the relation with clinical outcome when presence of CTC identified with different technologies are reported, as different CTC subpopulations can have different relations with clinical outcome.


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