High CDKN2A/p16 and low FGFR3 expression predict progressive potential of stage pT1 urothelial bladder carcinoma
Background - A recent study on the comprehensive genomic profile of advanced urothelial bladder cancer (UBC) showed cyclin-dependent kinase inhibitor 2A (CDKN2A) and fibroblast growth factor receptor 3 (FGFR3) as the most often clinically relevant genomic alterations. Therefore, the prognostic role...
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| Main Authors: | , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
Feb 2, 2018
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| In: |
Clinical genitourinary cancer
Year: 2018, Volume: 16, Issue: 4, Pages: 248-256.e2 |
| ISSN: | 1938-0682 |
| DOI: | 10.1016/j.clgc.2018.01.009 |
| Online Access: | Verlag, Volltext: https://doi.org/10.1016/j.clgc.2018.01.009 Verlag, Volltext: http://www.sciencedirect.com/science/article/pii/S1558767318300363 
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| Author Notes: | Johannes Breyer, Ralph M. Wirtz, Philipp Erben, Thomas S. Worst, Robert Stoehr, Markus Eckstein, Simone Bertz, Danijel Sikic, Stefan Denzinger, Maximilian Burger, Arndt Hartmann, Wolfgang Otto, Johannes Breyer, Ralph M. Wirtz, Philipp Erben, Thomas S. Worst, Robert Stoehr, Markus Eckstein, Danijel Sikic, Maximilian Burger, Arndt Hartmann, Wolfgang Otto |
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| 245 | 1 | 0 | |a High CDKN2A/p16 and low FGFR3 expression predict progressive potential of stage pT1 urothelial bladder carcinoma |c Johannes Breyer, Ralph M. Wirtz, Philipp Erben, Thomas S. Worst, Robert Stoehr, Markus Eckstein, Simone Bertz, Danijel Sikic, Stefan Denzinger, Maximilian Burger, Arndt Hartmann, Wolfgang Otto, Johannes Breyer, Ralph M. Wirtz, Philipp Erben, Thomas S. Worst, Robert Stoehr, Markus Eckstein, Danijel Sikic, Maximilian Burger, Arndt Hartmann, Wolfgang Otto |
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| 520 | |a Background - A recent study on the comprehensive genomic profile of advanced urothelial bladder cancer (UBC) showed cyclin-dependent kinase inhibitor 2A (CDKN2A) and fibroblast growth factor receptor 3 (FGFR3) as the most often clinically relevant genomic alterations. Therefore, the prognostic role of FGFR3 and CDKN2A/p16 for pT1 UBC was studied. - Patients and Methods - Clinical data and formalin-fixed paraffin-embedded tissues of pT1 UBC treated with an organ-preserving approach was analyzed retrospectively. Total RNA was isolated using commercial RNA extraction kits and mRNA expression of CDKN2A/p16 and FGFR3 was measured using single step reverse transcription quantitative real time polymerase chain reaction using RNA-specific TaqMan assays. - Results - Data from 296 patients (79.4% male; median age: 72 years) could be used for the final evaluation. Spearman correlation revealed a statistically significant negative correlation between mRNA expression of CDKN2A/p16 and FGFR3. There was a positive correlation between CDKN2A/p16 and G3 tumors (ρ = 0.1875; P = .0012) and associated carcinoma in situ (ρ = 0.1703, P = .0033) and a negative correlation between FGFR3 and these factors (ρ = −0.2791, P < .0001 and ρ = −0.2182, P = .0002). High CDKN2A/p16 expression (≥38.04) and low FGFR3 expression (<39.14) were statistically significantly associated with worse progression-free survival (PFS; P = .0194 and P = .0089). Multivariate Cox regression analysis could identify patients with low FGFR3 and high CDKN2A/p16 expression (log rank (LR) χ2 = 10.69; P = .0048) as well as tumor size ≥3 cm (LR χ2 = 6.03; P = .0141) as independent predictors for PFS. - Conclusion - High expression of CDKN2A/p16 and low expression of FGFR3 show a correlation with established prognostic features for non–muscle-invasive bladder cancer and can predict progression of stage pT1 UBC. | ||
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