title: Telomerase reverse transcriptase (TERT) promoter mutation analysis of benign, malignant and reactive urothelial lesions reveals a subpopulation of inverted papilloma with immortalizing genetic change.
abstract: OBJECTIVE
  To understand more clearly the genetic ontogeny of inverted papilloma of urinary bladder, we analysed telomerase reverse transcriptase (TERT) promoter mutation status in a group of 26 inverted papillomas in comparison with the mutation status of urothelial carcinoma with inverted growth (26 cases), conventional urothelial carcinoma (36 Ta non-invasive urothelial carcinoma, 35 T2 invasive urothelial carcinoma) and cystitis glandularis (25 cases).
  
  
  RESULTS
  TERT promoter mutations in inverted papilloma, urothelial carcinoma with inverted growth, urothelial carcinoma and cystitis glandularis were found in 15% (four of 26), 58% (15 of 26), 63% (45 of 71) and 0% (none of 25), respectively. C228T mutations were the predominant mutations (97%) found in bladder tumours, while C250T aberrations occurred in approximately 3% of bladder tumours. In the inverted papilloma group, TERT mutation occurred predominantly in female patients (P = 0.006). Among urothelial carcinomas, TERT promoter mutation status did not correlate with gender, histological grade or pathological stage.
  
  
  CONCLUSIONS
  TERT promoter mutations were found in 15% of inverted papillomas. Our data suggest that there is a subpopulation of inverted papilloma that shares a carcinogenetic pathway with urothelial carcinoma with inverted growth and conventional urothelial carcinomas. Caution is warranted in exploring TERT promoter mutation status as a screening or adjunct diagnostic test for bladder cancer.
authors.affiliation: Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.|Department of Urology, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Liang
authors.initials: L
authors.lastname: Cheng
authors.affiliation: Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Darrell D
authors.initials: DD
authors.lastname: Davidson
authors.affiliation: Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Mingsheng
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Pathology, Unit of Anatomical Pathology, Cordoba, Spain.|Department of Surgery, Faculty of Medicine, Cordoba, Spain.|Champalimaud Clinical Center, Lisbon, Portugal.
authors.forename: Antonio
authors.initials: A
authors.lastname: Lopez-Beltran
authors.affiliation: Institute of Pathological Anatomy and Histopathology, School of Medicine, Polytechnic University of the Marche Region (Ancona), United Hospitals, Ancona, Italy.
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Montironi
authors.affiliation: Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.
authors.forename: Lisha
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Pathology, Singapore General Hospital, Singapore, Singapore.
authors.forename: Puay-Hoon
authors.initials: PH
authors.lastname: Tan
authors.affiliation: Department of Pathology, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Gregory T
authors.initials: GT
authors.lastname: MacLennan
authors.affiliation: Department of Pathology and Laboratory Medicine, Henry Ford Health System, Detroit, MI, USA.
authors.forename: Sean R
authors.initials: SR
authors.lastname: Williamson
authors.affiliation: Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Shaobo
authors.initials: S
authors.lastname: Zhang
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma / Q000175:diagnosis / Q000235:genetics*; D015331:Cohort Studies; D003556:Cystitis / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D018308:Papilloma, Inverted / Q000175:diagnosis / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D019098:Telomerase / Q000235:genetics*; D001743:Urinary Bladder / Q000473:pathology; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis / Q000235:genetics*; D019459:Urothelium / Q000473:pathology
chemical_list: D019098:Telomerase
keywords: TERT promoter mutation; carcinogenesis; differential diagnosis; inverted papilloma; inverted urothelial carcinoma; molecular genetics; urinary bladder