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Circulating Tumor Cells Count and Morphological Features in Breast, Colorectal and Prostate Cancer.doc

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Circulating Tumor Cells Count and Morphological Features in Breast, Colorectal and Prostate Cancer

CirculatingTumorCellsCountandMorphological FeaturesinBreast,ColorectalandProstateCancer SjoerdT.Ligthart1,FrankA.W.Coumans1,Francois-ClementBidard2,LiekeH.J.Simkens3, CornelisJ.A.Punt3,MarcoR.deGroot4,GerhardtAttard5,JohannS.deBono5,Jean-YvesPierga2, LeonW.M.M.Terstappen1* 1DepartmentofMedicalCellBioPhysics,MIRAInstitute,UniversityofTwente,Enschede,TheNetherlands,2DepartmentofMedicalOncology,InstitutCurie,Paris,France, 3Department of Medical Oncology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands, 4Department of Internal Medicine, Medisch SpectrumTwente,Enschede,TheNetherlands,5TheRoyalMarsdenNHSFoundationTrust,Sutton,Surrey,UnitedKingdom Abstract Background:Presenceofcirculatingtumorcells(CTC)inpatientswithmetastaticbreast,colorectalandprostatecanceris indicative for poor prognosis. An automated CTC (aCTC) algorithm developed previously to eliminate the variability in manualcountingofCTC(mCTC)wasusedtoextractmorphologicalfeatures.HerewevalidatedtheaCTCalgorithmonCTC images from prostate, breast and colorectal cancer patients and investigated the role of quantitative morphological parameters. Methodology:Storedimagesofsamplesfrompatientswithprostate,breastandcolorectalcancer,healthycontrols,benign breastandcolorectaltumorswereobtainedusingtheCellSearchsystem.ImageswereanalyzedforthepresenceofaCTC andtheirmorphologicalparametersmeasuredandcorrelatedwithsurvival. Results: Overall survival hazard ratio was not significantly different for aCTC and mCTC. The number of CTC correlated strongestwithsurvival,whereasCTCsize,roundnessandapoptosisfeaturesreachedsignificanceinunivariateanalysis,but notinmultivariateanalysis.OneaCTC/7.5mlofbloodwasfoundin7of204healthycontrolsand9of694benigntumors.In onepatientwithbenigntumor2andanother9aCTCweredetected. Significanceofthestudy:CTCcanbeidentifiedandmorphologicalfeaturesextractedbyanalgorithmonimagesstoredby theCellSearchsystemandstronglycorrelatewithclinicaloutcomeinmetastaticbreast,colorectalandpro