Fibroblast growth factor receptor (FGFR) gene amplifications are rare events in bladder cancer. Issue 5 (12th January 2015)

• Record Type: Journal Article
• Authors: Fischbach, Anna; Rogler, Anja; Erber, Ramona; Stoehr, Robert; Poulsom, Richard; Heidenreich, Axel; Schneevoigt, Birte‐Swantje; Hauke, Sven; Hartmann, Arndt; Knuechel, Ruth; Veeck, Jürgen; Gaisa, Nadine T
• Is Part Of: Histopathology. Volume 66:Issue 5(2015)
• Page Start: 639
• Page End: 649
• Publication Date: 2015-01-12
• Subjects: Histology, Pathological -- Periodicals; 611.018
• DOI: 10.1111/his.12473
• Languages: English
• ISSNs: 0309-0167

Abstract

<abstract abstract-type="main" id="his12473-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="his12473-sec-0001" sec-type="section"> <title>Aims</title> <p>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 <italic>FGFR1‐3</italic> by fluorescence <italic>in‐situ</italic> hybridization (FISH).</p> </sec> <sec id="his12473-sec-0002" sec-type="section"> <title>Methods and results</title> <p>Tumours of 153 patients (<italic>n </italic>=<italic> </italic>65 pTa low‐grade, <italic>n </italic>=<italic> </italic>15 pTa high‐grade, <italic>n </italic>=<italic> </italic>37 pT1, <italic>n </italic>=<italic> </italic>20 pT2, <italic>n </italic>=<italic> </italic>10 pT3, <italic>n </italic>=<italic> </italic>6 pT4) were analysed by FISH for <italic>FGFR1‐3</italic> copy numbers and screened for <italic>FGFR3</italic> mutations and immunohistochemical protein expression. Amplifications of <italic>FGFR1</italic> were found in 1.6% (two of 122), <italic>FGFR2</italic> in 0.8% (one of 121) and <italic>FGFR3</italic> 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 <italic>FGFR3</italic>‐amplified samples showed concomitant <italic>FGFR3</italic> mutations and FGFR3 protein overexpression. <italic>FGFR</italic> amplifications were not associated significantly with gender, age, grade or stage in statistical analyses.</p> </sec> <sec id="his12473-sec-0003" sec-type="section"> <title>Conclusions</title> <p> <italic>FGFR</italic> amplifications are rare events in bladder cancer, with <italic>FGFR3</italic> amplification being the most prevalent (3.4% of cases). Concomitant <italic>FGFR3</italic> 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.</p> </sec> </abstract>