Mp65-09 molecular tumour grading and outcome prognostication of non muscle invasive bladder cancer based on whole transcriptome analysis

You have accessJournal of UrologyBladder Cancer: Basic Research & Pathophysiology III1 Apr 2017MP65-09 MOLECULAR TUMOUR GRADING AND OUTCOME PROGNOSTICATION OF NON MUSCLE INVASIVE BLADDER CANCER BASED ON WHOLE TRANSCRIPTOME ANALYSIS Alexandre R Zlotta, Jess Shen, Aidan P Noon, Haiyan Jiang, Cynthia Kuk, Ruoyu Ni, Balram Sukhu, Kin Chan, Annette Erlich, Morgan Roupret, Thomas Seisen, Eva Comparat, Joan Sweet, Girish S Kulkarni, Neil E Fleshner, Azar Azad, Theodorus H van der Kwast, and Jeffrey Wrana Alexandre R ZlottaAlexandre R Zlotta More articles by this author , Jess ShenJess Shen More articles by this author , Aidan P NoonAidan P Noon More articles by this author , Haiyan JiangHaiyan Jiang More articles by this author , Cynthia KukCynthia Kuk More articles by this author , Ruoyu NiRuoyu Ni More articles by this author , Balram SukhuBalram Sukhu More articles by this author , Kin ChanKin Chan More articles by this author , Annette ErlichAnnette Erlich More articles by this author , Morgan RoupretMorgan Roupret More articles by this author , Thomas SeisenThomas Seisen More articles by this author , Eva ComparatEva Comparat More articles by this author , Joan SweetJoan Sweet More articles by this author , Girish S KulkarniGirish S Kulkarni More articles by this author , Neil E FleshnerNeil E Fleshner More articles by this author , Azar AzadAzar Azad More articles by this author , Theodorus H van der KwastTheodorus H van der Kwast More articles by this author , and Jeffrey WranaJeffrey Wrana More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.2003AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Non muscle invasive bladder cancer (NMIBC) has a highly variable clinical behaviour not adequately predicted by their histological grade and clinical parameters. Some are indolent; others quickly progress to muscle-invasive disease. The discrepancy between phenotype and genotype is compounded further by interobserver variability in pathological grading. METHODS Whole transcriptomic (WT) analysis of 178 bladder tumours (158 NMIBC and 20 MIBC or metastatic) was performed from formalin fixed paraffin embedded (FFPE) tissues incorporating messenger RNA expression, splice variants, gene fusion and mutation detection. In NMIBC, we used a discovery (n=38) and 2 validation cohorts (n= 40 and 80). These data were integrated and tested for correlations with both pathological grading and clinical outcomes. Conventional pathological grading for both WHO 1973 (grade 1, 2 and 3) and 2004 (low grade-LG vs high grade-HG) classifications was reviewed by 3 different expert uro-pathologists and kappa statistic for interobserver variability was calculated. RESULTS Unsupervised clustering of data from RNA sequencing revealed classification of three robust-non-overlapping molecular subtypes of NMIBC termed Grade Related Index (GRI) 1, GRI2 and GRI3. GRI1 comprised of almost exclusively LG tumours, while GRI3 clustered with HG MIBC tumours. After assessment by expert pathologists, kappa for interobserver variability in 1973 WHO histological grading was 0.40 whereas it reached 0.78 for the 2004 classification. Most discrepant cases clustered in molecular subtype GRI2. GRI subclassification independently predicted disease progression in NMIBC (p=0.004, gray test). FGFR3 mutations, FGFR3::TACC3 fusion events and Hedgehog were strongly enriched in GRI1. GRI3 disease was associated with a germ stem cell-like phenotype and upregulation in APOBEC3B. CONCLUSIONS WT sequencing data delineated three molecular classes of NMIBC, and improved prediction of disease progression from NMIBC to MI compared to conventional histologic grading. WT analysis could be integrated to a new WHO classification. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e855-e856 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Alexandre R Zlotta More articles by this author Jess Shen More articles by this author Aidan P Noon More articles by this author Haiyan Jiang More articles by this author Cynthia Kuk More articles by this author Ruoyu Ni More articles by this author Balram Sukhu More articles by this author Kin Chan More articles by this author Annette Erlich More articles by this author Morgan Roupret More articles by this author Thomas Seisen More articles by this author Eva Comparat More articles by this author Joan Sweet More articles by this author Girish S Kulkarni More articles by this author Neil E Fleshner More articles by this author Azar Azad More articles by this author Theodorus H van der Kwast More articles by this author Jeffrey Wrana More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...