Mutter-de Wit, Sanne

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EpCAM+ and EpCAM– circulating tumor cells in metastatic cancer patients: a multicenter study

University of Twente Research Information

CTC-TrapAbstract 3787AACR  2017SurvivalDetection of CTCConclusionEpCAM antigens per cell EpCAM+ CTCrecovery UnaccountedEpCAM- CTC recovery SizePC3 1.0x104 27% 52% 21% 18 µmMDA-MB-231 1.5x104 26% 56% 18% 16 µmPROSTATE CANCER PATIENTS• Mean EpCAM+ CTC: 124 CTC (n=106, min 0-max 3300) • Mean EpCAM- CTC: 3 CTC (n=93, min 0-max 24)• EpCAM+ CTC ≥5 = 53%EpCAM- CTC ≥5  = 28%• Using EpCAM+ and EpCAM-for ≥5 CTC: detection of patients increases to 70%BREAST CANCER PATIENTS• Mean EpCAM+ CTC: 13 CTC (n=22, min 0-max 208) • Mean EpCAM- CTC: 8 CTC (n=22, min 0-max 35)• EpCAM+ CTC ≥5 = 32%EpCAM- CTC ≥5  = 36%• Using EpCAM+ and EpCAM-for ≥5 CTC: detection of patients increases to 64%CELL LINE RECOVERYProstate (PC3) and breast (MDA-MB-231) cancer cell lines were used for spiking in healthycontrols at 3 separate occasions and processed at 6 different sites to validate the procedure.Patients from 6 clinical sites in the EuropeanCTC-Trap consortium were enrolled (a) in thestudy for detection of EpCAM+ CTC (byCellSearch) (b) and EpCAM- CTC (by filtration)(c), followed by quantification (d) and reviewanalysis with the program ACCEPT (e).Evaluation of CTCCTC DEFINITION• EpCAM+ CTC: DAPI+, cytokeratin+, CD45-, round, >4μm in size, DAPI-CK overlay >50%• EpCAM- CTC: DAPI+, cytokeratin+, CD45-, DAPI-CK overlayClinical outcome was determinedfor 64 prostate cancer patients.Presence of EpCAM+ CTC is significantly associated with poor overall survivalPresence of EpCAM- CTC is not associated with poor overall survivalutwente.nl/tnw/ctctraputwente.nl/tnw/mcbp/protocolsandtoolsResearch funded by EU FP7-HEALTH-2012.1.2-1 Project #305341S. de Wit et al. 10.1038/srep12270 (2015)• In a multicenter study EpCAM+ CTC andEpCAM- CTC were detected in mPC and mBCpatients.• EpCAM+ CTC are associated with poor overallsurvival in mPC, but EpCAM- CTC are not.• The clinical value of EpCAM- CTC in mPCremains questionable.EpCAM+ CTC are strongly associated with poorprognosis for patients. We investigated thepresence of EpCAM- CTC in metastatic prostatecancer (mPC) and metastatic breast cancer(mBC) patients and related their presence withoverall survival.EpCAM+ and EpCAM- circulating tumor cells in metastatic cancer patients: a multicenter studySanne de Wit1, M. Manicone2, E. Rossi2,3, E.K. Trapp4, R. Lampignano6, M. Ouhlen7,8, M. Crespo10, L.L Zeune1, K.C. Andree1, J.F. Swennenhuis1, R. Vidotto2, R. Zamarchi2, M. Alunni-Fabbroni4, M. Tzschaschel5, B. Rack4, H. Neubauer6, T. Fehm6, E. Colomba9, F. Farace7,8, P. Flohr10, J. De Bono10,11, L.W.M.M. Terstappen11 Department of Medical Cell BioPhysics, University of Twente, the Netherlands, 2 IOV-IRCCS, Padova, Italy, 3 DiSCOG – University of Padova, Italy, 4 Department of Gynecology and Obstetrics, Ludwig-Maximilian-University, Germany, 5 Department of Gynecology and Obstetrics, Ulm-University, Germany, 6 Department of Obstetrics and Gynecology, Heinrich-Heine-University, Germany, 7 “CTC” Translational Platform, Gustave Roussy, Université Paris-Saclay, France, 8 “Identification of Targets for Cancer Treatment”, Université Paris-Saclay , France, 9 Department of Medicine, Gustave Roussy, Université Paris-Saclay, France, 10 Cancer Biomarkers, The Institute of Cancer Research, United Kingdom, 11 Prostate Cancer Targeted Therapy Group, The Institute of Cancer Research, United Kingdom. s.dewit@utwente.nl0204060801001 2 3 4 5 6 7Score of objects for CTC consensus Category 1 Category 2 Category 3 Category 4A collection of 100 objects were independentlyreviewed by 7 operators to determine consensusof scoring EpCAM+ and EpCAM- CTC . For 19 of theobjects operators were divided whether the objectwas a CTC or not. For 5 objects all operators werein complete agreement it definitely being a CTC.

EpCAM+ and EpCAM– circulating tumor cells in metastatic cancer patients: a multicenter study

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