MP57-09 MOLECULAR PROFILING OF SMALL CELL BLADDER CANCER: IMPLICATIONS FOR IMMUNOTHERAPEUTIC STRATEGIES (2019)

You have accessJournal of UrologyBladder Cancer: Basic Research & Pathophysiology II (MP57)1 Apr 2019MP57-09 MOLECULAR PROFILING OF SMALL CELL BLADDER CANCER: IMPLICATIONS FOR IMMUNOTHERAPEUTIC STRATEGIES Bryan A Smith, Nikolas G Balanis, Brandon Tsai, Jung-Wook Park, Hanwei Zhang, Jonathan W Said, Thomas G Graeber, Owen N Witte, and Arnold I Chin* Bryan A SmithBryan A Smith More articles by this author , Nikolas G BalanisNikolas G Balanis More articles by this author , Brandon TsaiBrandon Tsai More articles by this author , Jung-Wook ParkJung-Wook Park More articles by this author , Hanwei ZhangHanwei Zhang More articles by this author , Jonathan W SaidJonathan W Said More articles by this author , Thomas G GraeberThomas G Graeber More articles by this author , Owen N WitteOwen N Witte More articles by this author , and Arnold I Chin*Arnold I Chin* More articles by this author View All Author Informationhttps://doi.org/10.1097/01.JU.0000556626.19138.d3AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVES: Small cell bladder cancer is a rare yet highly lethal histological variant that lacks viable treatment options. High-throughput genomic analyses have shed light into driver alterations and therapeutic targets for bladder cancer. Molecular information is lacking for the small cell phenotype. METHODS: High-throughput RNA sequencing was performed on formalin fixed archived tissue from histologically defined small cell (n = 11) and urothelial (n = 10) muscle-invasive bladder cancer. Bioinformatic analyses were performed to identify enriched gene sets and transcriptional regulators specific for the respective cancer phenotypes. PD-L1 immunohistochemistry was performed on the bladder cancer cohort. To identify potential targets amenable to immunotherapeutic strategies, a computational analysis was utilized to mark cell surface markers overexpressed on small cell bladder cancer samples. A pan-small cell analysis identified cell surfaces markers potentially enriched in small cell cancer from other epithelial tissues. RESULTS: Clustering analyses separated small cell and non-small cell muscle-invasive bladder cancers into their respective histological phenotypes. Differential expression analysis between small cell and muscle invasive bladder cancer samples revealed overexpression of genes and transcription factors associated with neuronal development in the small cell phenotype. PD-L1 immunohistochemistry was expressed on approximately 80% (>1% PD-L1 expression) of our small cell bladder cancer samples with the expression confined to the tumor-infiltrated immune cells. Furthermore, we found that small cell bladder cancers overexpress a distinct set of cell surface markers compared to non-small cell neuroendocrine bladder cancers. Interestingly, a number of these cell surface markers were also overexpressed on small cell neuroendocrine cancers from the prostate and lung. CONCLUSIONS: Our findings shed light into the molecular mechanisms common to small cell bladder cancer and provide insight into potential immunotherapeutic targets to treat this aggressive malignancy. Source of Funding: Hal Gaba Broad Stem Center Research Center Innovation Award, Perkins Foundation Los Angeles, CA© 2019 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 201Issue Supplement 4April 2019Page: e816-e816 Advertisement Copyright & Permissions© 2019 by American Urological Association Education and Research, Inc.MetricsAuthor Information Bryan A Smith More articles by this author Nikolas G Balanis More articles by this author Brandon Tsai More articles by this author Jung-Wook Park More articles by this author Hanwei Zhang More articles by this author Jonathan W Said More articles by this author Thomas G Graeber More articles by this author Owen N Witte More articles by this author Arnold I Chin* More articles by this author Expand All Advertisement PDF downloadLoading ...