PD25-02 INTRATUMORAL HETEROGENEITY OF MOLECULAR SUBTYPES IN MUSCLE-INVASIVE BLADDER CANCER – AN EXTENSIVE MULTI-REGIONAL IMMUNOHISTOCHEMICAL ANALYSIS

Abstract

You have accessJournal of UrologyCME1 Apr 2023PD25-02 INTRATUMORAL HETEROGENEITY OF MOLECULAR SUBTYPES IN MUSCLE-INVASIVE BLADDER CANCER – AN EXTENSIVE MULTI-REGIONAL IMMUNOHISTOCHEMICAL ANALYSIS Simon Schallenberg, Mihnea Dragomir, Philipp Anders, Benedikt Ebner, Yannic Volz, Lennert Eismann, Severin Rodler, Jozefina Casuscelli, Alexander Buchner, Frederick Klauschen, Christian Stief, David Horst, and Gerald Schulz Simon SchallenbergSimon Schallenberg More articles by this author , Mihnea DragomirMihnea Dragomir More articles by this author , Philipp AndersPhilipp Anders More articles by this author , Benedikt EbnerBenedikt Ebner More articles by this author , Yannic VolzYannic Volz More articles by this author , Lennert EismannLennert Eismann More articles by this author , Severin RodlerSeverin Rodler More articles by this author , Jozefina CasuscelliJozefina Casuscelli More articles by this author , Alexander BuchnerAlexander Buchner More articles by this author , Frederick KlauschenFrederick Klauschen More articles by this author , Christian StiefChristian Stief More articles by this author , David HorstDavid Horst More articles by this author , and Gerald SchulzGerald Schulz More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003303.02AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Molecular bladder cancer (BC) subtypes define distinct biological entities and were shown to predict treatment response in neoadjuvant and adjuvant setting. The extent of intratumoral heterogeneity (ITH) might affect subtyping of individual patients. This study intended to comprehensively asses ITH in a cohort of muscle-invasive BC. METHODS: 251 patients undergoing radical cystectomy were screened. Three cores of the tumor center (TC) and 3 cores of the invasive tumor front (TF) of each patient were assembled in a tissue-microarray. Molecular subtypes were determined employing 12 pre-evaluated immunohistochemical markers (FGFR3, CCND1, RB1, CDKN2A, KRT5, KRT14, FOXA1, GATA3, TUBB2B, EPCAM, CDH1, Vimentin). A total of 18,072 spots were evaluated of which 15,002 spots were assessed based on intensity, distribution or the combination. Allocation to one of 5 different molecular subtypes: Urothelial-like (Uro); Genomically Unstable (GU); Small-cell/Neuroendocrine-like (Sc/NE-like); Basal/SCC-like (Basal); Mesenchymal-like (Mes) was conducted for each patient for the complete tumor, individual cores, TF, and TC separately. Primary objective: ITH between TF and TC (n=208 patients). Secondary objective: Multi-region ITH (n=191 patients). Analysis of the composition of ITH-cases, correlation with clinicopathological parameters, and prognosis. RESULTS: Subtyping of the complete cohort revealed Uro: 37.1%, GU: 34.3%, Sc/NE-like: 8.8%, Basal/SCC-like: 18.7%, and Mesenchymal-like: 1.2%. ITH between TF and TC was seen in 12.5% (n=26/208) and ITH defined by at least two different subtypes of any location in 24.6% (n=47/191). ITH was more frequent in locally confined (pT2) vs. advanced (pT≥3) BC stages (38.7% vs. 21.9%, p=0.046). pT4 BC presented with significantly more basal subtypes compared to pT2 BC (26.2% vs. 11.5%, p=0.049). There was no correlation of ITH with prognosis or molecular subtypes. CONCLUSIONS: Several molecular subtypes can be found in nearly every fourth case of muscle-invasive BC. ITH must be given due consideration for individualized, subtype-based therapeutic approaches. Source of Funding: university internal funds, no external funding © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e729 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Simon Schallenberg More articles by this author Mihnea Dragomir More articles by this author Philipp Anders More articles by this author Benedikt Ebner More articles by this author Yannic Volz More articles by this author Lennert Eismann More articles by this author Severin Rodler More articles by this author Jozefina Casuscelli More articles by this author Alexander Buchner More articles by this author Frederick Klauschen More articles by this author Christian Stief More articles by this author David Horst More articles by this author Gerald Schulz More articles by this author Expand All Advertisement PDF downloadLoading ...