title: Fibroblast growth factor receptor (FGFR) gene amplifications are rare events in bladder cancer.
abstract: OBJECTIVE
  Activating point mutations and protein overexpression of fibroblast growth factor receptors (FGFRs), especially FGFR3, are frequent events in bladder cancer. Little is known about gene amplifications, therefore we characterized amplification of FGFR1-3 by fluorescence in-situ hybridization (FISH).
  
  
  RESULTS
  Tumours of 153 patients (n = 65 pTa low-grade, n = 15 pTa high-grade, n = 37 pT1, n = 20 pT2, n = 10 pT3, n = 6 pT4) were analysed by FISH for FGFR1-3 copy numbers and screened for FGFR3 mutations and immunohistochemical protein expression. Amplifications of FGFR1 were found in 1.6% (two of 122), FGFR2 in 0.8% (one of 121) and FGFR3 in 3.4% (five of 145). All amplifications were high-level amplifications, not overlapping with polysomy. Amplifications were found in papillary/papillary-invasive tumour parts, and predominantly in tumours with enhanced Ki67 index (>10%), aberrant CK20 expression, and low p53 expression. All FGFR3-amplified samples showed concomitant FGFR3 mutations and FGFR3 protein overexpression. FGFR amplifications were not associated significantly with gender, age, grade or stage in statistical analyses.
  
  
  CONCLUSIONS
  FGFR amplifications are rare events in bladder cancer, with FGFR3 amplification being the most prevalent (3.4% of cases). Concomitant FGFR3 mutations and protein overexpression indicate that FGFR3-mediated signalling in these tumours would probably be highly active. This patient subgroup may be particularly suited to FGFR-targeted pharmacotherapy.
authors.affiliation: Institute of Pathology, RWTH Aachen University, Aachen, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Fischbach
authors.forename: Anja
authors.initials: A
authors.lastname: Rogler
authors.forename: Ramona
authors.initials: R
authors.lastname: Erber
authors.forename: Robert
authors.initials: R
authors.lastname: Stoehr
authors.forename: Richard
authors.initials: R
authors.lastname: Poulsom
authors.forename: Axel
authors.initials: A
authors.lastname: Heidenreich
authors.forename: Birte-Swantje
authors.initials: BS
authors.lastname: Schneevoigt
authors.forename: Sven
authors.initials: S
authors.lastname: Hauke
authors.forename: Arndt
authors.initials: A
authors.lastname: Hartmann
authors.forename: Ruth
authors.initials: R
authors.lastname: Knuechel
authors.forename: Jürgen
authors.initials: J
authors.lastname: Veeck
authors.forename: Nadine T
authors.initials: NT
authors.lastname: Gaisa
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D005260:Female; D005784:Gene Amplification / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics*; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000235:genetics*; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000235:genetics*; D046888:Tissue Array Analysis; D001749:Urinary Bladder Neoplasms / Q000235:genetics*; D055815:Young Adult
chemical_list: C496348:FGFR1 protein, human; C496353:FGFR2 protein, human; C496365:FGFR3 protein, human; D051496:Receptor, Fibroblast Growth Factor, Type 1; D051497:Receptor, Fibroblast Growth Factor, Type 2; D051498:Receptor, Fibroblast Growth Factor, Type 3
keywords: FGFR1; FGFR2; FGFR3; amplification; bladder cancer