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; Leonardus Wendelinus Mathias Marie Terstappen

doi:10.18632/oncotarget.26298

EpCAM^high and EpCAM^low circulating tumor cells in metastatic prostate and breast cancer patients

Oncotarget. 2018 Nov 2;9(86):35705-35716. doi: 10.18632/oncotarget.26298.

Authors

Sanne de Wit¹, Mariangela Manicone², Elisabetta Rossi^{2

3}, Rita Lampignano⁴, Liwen Yang⁴, Beate Zill⁵, Alvera Rengel-Puertas⁵, Marianne Ouhlen^{6

7}, Mateus Crespo⁸, Anne Margreet Sofie Berghuis⁹, Kiki Carlijn Andree¹, Riccardo Vidotto², Elisabeth Katharina Trapp⁵, Marie Tzschaschel¹⁰, Emeline Colomba¹¹, Gemma Fowler⁸, Penelope Flohr⁸, Pasquale Rescigno^{8

12}, Mariane Sousa Fontes^{8

12}, Rita Zamarchi², Tanja Fehm⁴, Hans Neubauer⁴, Brigitte Rack⁵, Marianna Alunni-Fabbroni⁵, Françoise Farace^{6

7}, Johann De Bono^{8

12}, Maarten Joost IJzerman⁹, Leonardus Wendelinus Mathias Marie Terstappen¹

Affiliations

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.

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.

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