Contents lists available at ScienceDirect Surgical Oncology journal homepage: www.elsevier.com/locate/suronc The prognostic signifcance of positive peritoneal cytology in endometrial cancer and its correlations with L1-CAM biomarker Enrico Vizza a , Emanuela Mancini a , Valentina Laquintana b ,RossellaLoria b , Mariantonia Carosi c , Ermelinda Baiocco a , Lucia Cicchillitti a , Giulia Piaggio b , Lodovico Patrizi d , Isabella Sperduti e , Ashanti Zampa a , Giuseppe Cutillo a , Rita Falcioni b,1 , Giacomo Corrado f,∗,1 a Department of Experimental Clinical Oncology, Gynecologic Oncology Unit, IRCCS "Regina Elena" National Cancer Institute, Rome, Italy b Department of Research, Advanced Diagnostics and Technological Innovation, Area of Translational Research, IRCCS “Regina Elena” National Cancer Institute, Rome, Italy c Department of Research, Advanced Diagnostics and Technological Innovation, Anatomy Pathology Unit IRCCS “Regina Elena” National Cancer Institute, Rome, Italy d Department of Biomedicine and Prevention, Obstetrics and Gynecology Unit, University of Rome "Tor Vergata", Rome, Italy e Scientific Direction, IRCCS “Regina Elena” National Cancer Institute, Rome, Italy f Department of Women and Children Health, Gynecologic Oncology Unit, Fondazione Policlinico Universitario A. Gemelli – IRCCS, Rome, Italy ARTICLEINFO Keywords: Endometrial cancer Peritoneal cytology L1CAM ABSTRACT Background: Theaimofthisstudywastoevaluatetheprognosticroleofpositiveperitonealcytology(PPC)ina cohort of patients with endometrial cancer (EC). The secondary objective was to correlate the PPC and the expression of L1CAM in a group of patients with recurrence endometrial disease. Methods: All women diagnosed with EC and who performed a peritoneal cytology at “Regina Elena” National CancerInstituteofRomefrom2001to2013wereincludedinthestudy.Patientsweredividedintotwogroups accordingtopositivityatperitonealcytology.Moreover,patientswitharecurrencediseaseandwhoseatissue microarray (TMA) tumor sample was available underwent a L1CAM analysis. Results: Seven hundred sixty six patients underwent to EC staging in our Institute: 696 (90.8%) with negative and 70 (9.2%) with positive cytology. Five-year recurrence rate was higher in women with PPC (46.9% vs 18.4%,p=0<0.0001)and,inparticular,distantrecurrence(86.7%vs53.4%,p=0.03).Moreover,wefound aninterestingpatternofrecurrencediseaseinthegroupofearlystageofECwithNPCandpositiveL1CAM. Conclusions: OurresultssupportthedatathatPPCmaybeapotentialprognosticfactorinearlyEC,duetoits signifcantassociationwithotherrisk factorsanditssignifcantinfuenceonsurvival.Our fndingsconfrmthe needforlargestudiesthatpointouttheroleofPPCandnewprognosticfactors,includingbiomarkersasL1CAM. 1. Introduction Despiteoptimalprognosisofpatientswithearlyendometrialcancer (EC),witha10-yearoverallsurvivalratehigherthan80%,asubstantial number of patients experience recurrence with a poor survival rate, where available prognostic factors are not able to predict this poor clinical outcome [1]. The prognostic value of peritoneal cytology was initially evaluated by Creasman and Rutledge in 1971. Through a co- hortof183patients,theauthorsdemonstratedworsesurvivalat4years for patients with positive cytology as compared to patients with nega- tivecytology.Theyalsoshowedthattheimpactofpositivecytologyon overall survival was maintained even in patients with carcinoma limitedtotheuterus[2].Although,alimitednumberofstudiesshowed that peritoneal positive cytology (PPC) could be an independent risk factorforadverseendometrialcanceroutcome,severalreportsfailedto demonstrate a negative correlation between PPC and overall survival (OS) or disease free survival (DFS) in patients with early endometrial cancer[3,4].Furtherstudies,alsoevaluatedtheroleofPPCcorrelated to other adverse prognostic factors such as grade, lymphovascular in- vasion and myometrial infltration with conficting results [5–8]. This uncertainty about the clinical and prognostic value of PPC resulted in theexclusionofperitonealcytologyfromtherevised2009International Federation of Gynecology and Obstetrics (FIGO) staging criteria for endometrial cancer, even though peritoneal cytology continues to be https://doi.org/10.1016/j.suronc.2019.01.001 Received7August2018;Receivedinrevisedform28November2018;Accepted2January2019 ∗ Correspondingauthor.DepartmentofWomanandChildHealth,GynecologicOncologyUnit,CatholicUniversityofSacredHeart,L.goA.Gemelli8,00168,Rome, Italy. E-mail address: giacomo.corrado@policlinicogemelli.it (G. Corrado). 1 Co-last authors. Surgical Oncology 28 (2019) 151–157 0960-7404/ © 2019 Elsevier Ltd. All rights reserved. T