High CDKN2A/p16 and Low FGFR3 Expression Predict Progressive Potential of Stage pT1 Urothelial Bladder Carcinoma
Breyer J, Wirtz RM, Erben P, Worst TS, Stoehr R, Eckstein M, Bertz S, Sikic D, Denzinger S, Burger M, Hartmann A, Otto W (2018)
Publication Type: Journal article
Publication year: 2018
Journal
DOI: 10.1016/j.clgc.2018.01.009
Abstract
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.
Authors with CRIS profile
Markus Eckstein
Institute of Pathology
Simone Bertz
Institute of Pathology
Arndt Hartmann
Lehrstuhl für Allgemeine Pathologie und Pathologische Anatomie
Involved external institutions
Universität Regensburg
Germany (DE)
Ruprecht-Karls-Universität Heidelberg
Germany (DE)
STRATIFYER Molecular Pathology GmbH
Germany (DE)
Germany (DE)
Ruprecht-Karls-Universität Heidelberg
Germany (DE)
STRATIFYER Molecular Pathology GmbH
Germany (DE)
How to cite
APA:
Breyer, J., Wirtz, R.M., Erben, P., Worst, T.S., Stoehr, R., Eckstein, M.,... Otto, W. (2018). High CDKN2A/p16 and Low FGFR3 Expression Predict Progressive Potential of Stage pT1 Urothelial Bladder Carcinoma. Clinical Genitourinary Cancer. https://doi.org/10.1016/j.clgc.2018.01.009
MLA:
Breyer, Johannes, et al. "High CDKN2A/p16 and Low FGFR3 Expression Predict Progressive Potential of Stage pT1 Urothelial Bladder Carcinoma." Clinical Genitourinary Cancer (2018).
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