PD36-01 NECTIN-4 PROTEIN EXPRESSION IN MUSCLE INVASIVE BLADDER CANCER - SELECTIVE PREDICTOR OR CONSISTENTLY EXPRESSED IN TUMOR TISSUE?

Abstract

You have accessJournal of UrologyCME1 Apr 2023PD36-01 NECTIN-4 PROTEIN EXPRESSION IN MUSCLE INVASIVE BLADDER CANCER - SELECTIVE PREDICTOR OR CONSISTENTLY EXPRESSED IN TUMOR TISSUE? Sebastian Jersinovic, Jörg Hennenlotter, Carmen Wandel, Sieglinde Baisch, Thomas Lütfrenk, Falko Fend, Tilman Todenhöfer, Arnulf Stenzl, and Steffen Rausch Sebastian JersinovicSebastian Jersinovic More articles by this author , Jörg HennenlotterJörg Hennenlotter More articles by this author , Carmen WandelCarmen Wandel More articles by this author , Sieglinde BaischSieglinde Baisch More articles by this author , Thomas LütfrenkThomas Lütfrenk More articles by this author , Falko FendFalko Fend More articles by this author , Tilman TodenhöferTilman Todenhöfer More articles by this author , Arnulf StenzlArnulf Stenzl More articles by this author , and Steffen RauschSteffen Rausch More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003334.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Nectin-4, a membrane protein involved in cell adhesion, has been recently introduced as a target of the novel antibody drug conjugate Enfortumab-Vedotin (EV). However, uniform Nectin-4 overexpression in BC was reported and no predictive capacity from Nectin-4 staining was reported. In the present trial we aimed to determine expression in two independent BC cohorts and further evaluate an alternative IHC interpretation approach for Nectin-4 in advanced BC. METHODS: The study included two independent cohorts consisting of n=97 and 103 patients (70x male, median age 65.5 years, 31x T≤2 – 43x T3 – 23x T4, 76x G>2, 11x M1 and 79x male, 69 years, 31x T≤2 – 48x T3 – 24x T4, 78x G>2, 9x M1, median follow-up 44.5 months, respectively) who underwent radical cystectomy for invasive BC. Tissues from histologically proven BC and from benign urothelium (n=22 and 39) were processed to a tissue microarray and immunohistochemically stained by reported methods (polyclonal rabbit antibody, dilution 1:2000, incubation 16h at 4°, quantified by the histochemical scoring system/H-score 0-300). Results were transferred into four classes: Each cohort was divided into four 25%-classes of successive increasing staining and distribution was demonstrated for each the two BC cohorts. Results were compared to clinical and pathological features. RESULTS: Mean expression scores in BC and parallel benign urothelium tissue were 133 and 81/157 and 114 (p<0.005/0.002) with benign urothelium expression correlated with that of corresponding BC (<0.02). The expressions within each patient cohort are lined up as follows: Expression in 25% of the cohort scored low (0-99), of 25% 100-119, of 25% 120-189 and of 25% strong (190-300) in the first cohort, the second distributed low (0-99) of 25%, 25% 100-165, 25% 166-209 and 25% strong 210-300. There were no significant associations of Nectin-4 expression to demographic or clinical patients’ data. Moreover, there was no clinical association between Nectin-4 expression and survival. CONCLUSIONS: Nectin-4 overexpression in BC is accompanied by parallel strong expressing benign urothelium in the same individual. While the distributions of expression in independent BC cohorts are similar, the assumption of Nectin-4 overexpression in all BC may be overestimated. A considerable share of even advanced BCs exhibit Nectin-4 only to a low or a medium level. This observation may support efforts of adapted reintroduction of Nectin-4 as a predictive biomarker for EV. Source of Funding: Sources of Funding are coming from University Hospital Tuebingen © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e980 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Sebastian Jersinovic More articles by this author Jörg Hennenlotter More articles by this author Carmen Wandel More articles by this author Sieglinde Baisch More articles by this author Thomas Lütfrenk More articles by this author Falko Fend More articles by this author Tilman Todenhöfer More articles by this author Arnulf Stenzl More articles by this author Steffen Rausch More articles by this author Expand All Advertisement PDF downloadLoading ...