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

// Sanne de Wit 1 , Mariangela Manicone 2 , Elisabetta Rossi 2, 3 , Rita Lampignano 4 , Liwen Yang 4 , Beate Zill 5 , Alvera Rengel-Puertas 5 , Marianne Ouhlen 6, 7 , Mateus Crespo 8 , Anne Margreet Sofie Berghuis 9 , Kiki Carlijn Andree 1 , Riccardo Vidotto 2 , Elisabeth Katharina Trapp 5 , Marie Tzschaschel 10 , Emeline Colomba 11 , Gemma Fowler 8 , Penelope Flohr 8 , Pasquale Rescigno 8, 12 , Mariane Sousa Fontes 8, 12 , Rita Zamarchi 2 , Tanja Fehm 4 , Hans Neubauer 4 , Brigitte Rack 5 , Marianna Alunni-Fabbroni 5 , Françoise Farace 6, 7 , Johann De Bono 8, 12 , Maarten Joost IJzerman 9 and Leonardus Wendelinus Mathias Marie Terstappen 1 1 Department of Medical Cell BioPhysics, Faculty of Sciences and Technology, MIRA Institute, University of Twente, Enschede, The Netherlands 2 Veneto Institute of Oncology IOV–IRCCS, Padova, Italy 3 DiSCOG–University of Padova, Padova, Italy 4 Department of Obstetrics and Gynecology, Heinrich-Heine-University, Düsseldorf, Germany 5 Department 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 8 Cancer Biomarkers, The Institute of Cancer Research, Sutton, United Kingdom 9 Department of Health Technology and Services Research, Faculty of Behavioural, Management and Social Sciences, MIRA Institute, University of Twente, Enschede, The Netherlands 10 Department of Gynecology and Obstetrics, Ulm-University, Munich, Germany 11 Department of Medicine, Gustave Roussy, Université Paris-Saclay, Villejuif, France 12 Prostate 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 (EpCAM high ) 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 (EpCAM low CTC). In the EU-FP7 CTC-Trap program, we investigated the presence of EpCAM high and EpCAM low CTC using CellSearch, followed by microfiltration of the EpCAM high 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 EpCAM high CTC and 28% had ≥5 EpCAM low CTC. For breast cancer patients, 32% had ≥5 EpCAM high CTC and 36% had ≥5 EpCAM low CTC. 70% of prostate cancer patients and 64% of breast cancer patients had in total ≥5 EpCAM high and/or EpCAM low CTC, increasing the number of patients in whom CTC are detected. Castration-resistant prostate cancer patients with ≥5 EpCAM high CTC had shorter overall survival versus those with <5 EpCAM high CTC ( p = 0.000). However, presence of EpCAM low 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.