Breyer, Johannes and Wirtz, Ralph M. and Erben, Philipp and Worst, Thomas S. and Stoehr, Robert and Eckstein, Markus and Bertz, Simone and Sikic, Danijel and Denzinger, Stefan and Burger, Maximilian and Hartmann, Arndt and Otto, Wolfgang (2018) High CDKN2A/p16 and Low FGFR3 Expression Predict Progressive Potential of Stage pT1 Urothelial Bladder Carcinoma. CLINICAL GENITOURINARY CANCER, 16 (4). 248-+. ISSN 1558-7673, 1938-0682
Full text not available from this repository. (Request a copy)Abstract
Identifying pT1 bladder cancer with high risk for progression remains a challenge. Aberrations in cyclin-dependent kinase inhibitor 2A (CDKN2A)/p16 and fibroblast growth factor receptor 3 (FGFR3) expression are the most common in urothelial bladder cancer. In the study at hand, we could show that high CDKN2A/p16 mRNA expression is associated with the luminal subtype and high CDKN2A/p16 as well as low FGFR3 mRNA expression are associated with worse progression-free survival. 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 formal in-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 (rho = 0.1875; P = .0012) and associated carcinoma in situ (rho = 0.1703, P = .0033) and a negative correlation between FGFR3 and these factors (rho = -0.2791, P < .0001 and rho = -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)chi(2) = 10.69; P = .0048) as well as tumor size >= 3 cm (LR chi(2) = 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | MESSENGER-RNA EXPRESSION; CELL-CARCINOMA; PROGNOSTIC VALUE; ALLELIC LOSSES; CANCER; RECURRENCE; VALIDATION; GUIDELINES; MUTATIONS; SURVIVAL; CDKN2A; mRNA; NMIBC; p16; Prognosis |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Urologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 12 Feb 2020 10:05 |
| Last Modified: | 12 Feb 2020 10:05 |
| URI: | https://pred.uni-regensburg.de/id/eprint/14180 |
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