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Updated: Apr 28, 2026
Author Spotlight: FISH as a Tool for Precise Gene Amplification Assessment in Cancer Specimens
Published on: July 12, 2024
Fibroblast growth factor receptor (FGFR) gene amplifications are rare events in bladder cancer
Anna Fischbach1, Anja Rogler, Ramona Erber
1Institute of Pathology, RWTH Aachen University, Aachen, Germany.
Aims:
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).
Methods And 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.
Insights
Fibroblast growth factor receptor (FGFR) gene amplifications are rare in bladder cancer, with FGFR3 amplification occurring in 3.4% of cases. These cases often show FGFR3 mutations and overexpression, suggesting potential benefit from FGFR-targeted therapies.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Activating mutations and protein overexpression of fibroblast growth factor receptors (FGFRs), particularly FGFR3, are common in bladder cancer.
- Gene amplifications of FGFRs are less understood, prompting investigation into their role.
Purpose of the Study:
- To characterize the amplification status of FGFR1-3 in bladder cancer using fluorescence in-situ hybridization (FISH).
- To correlate FGFR amplifications with tumor characteristics, including mutations, protein expression, and clinical parameters.
Main Methods:
- FISH analysis was performed on 153 bladder tumor samples to assess copy numbers of FGFR1-3.
- Samples were also screened for FGFR3 mutations and protein expression using immunohistochemistry.
- Tumor characteristics such as Ki67 index, CK20, and p53 expression were evaluated.
Main Results:
- FGFR1 amplification was found in 1.6%, FGFR2 in 0.8%, and FGFR3 in 3.4% of analyzed tumors.
- FGFR3 amplifications were high-level and occurred in papillary tumor components, often associated with high Ki67, aberrant CK20, and low p53 expression.
- All FGFR3-amplified tumors exhibited concurrent FGFR3 mutations and protein overexpression, but amplifications were not significantly linked to patient gender, age, grade, or stage.
Conclusions:
- FGFR amplifications are infrequent in bladder cancer, with FGFR3 amplification being the most common at 3.4%.
- The co-occurrence of FGFR3 amplification, mutation, and overexpression suggests highly active FGFR3-mediated signaling.
- This specific patient subgroup with FGFR3 alterations may be suitable candidates for FGFR-targeted pharmacotherapy.
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