Breyer, Johannes, Wirtz, Ralph M., Erben, Philipp ORCID: 0000-0002-8279-7636, Worst, Thomas S., Stoehr, Robert, Eckstein, Markus, Bertz, Simone, Sikic, Danijel, Denzinger, Stefan, Burger, Maximilian, Hartmann, Arndt and Otto, Wolfgang (2018). High CDKN2A/p16 and Low FGFR3 Expression Predict Progressive Potential of Stage pT1 Urothelial Bladder Carcinoma. Clin. Genitourin. Cancer, 16 (4). S. 248 - 259. DALLAS: CIG MEDIA GROUP, LP. ISSN 1938-0682

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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: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Breyer, JohannesUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wirtz, Ralph M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Erben, PhilippUNSPECIFIEDorcid.org/0000-0002-8279-7636UNSPECIFIED
Worst, Thomas S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stoehr, RobertUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Eckstein, MarkusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bertz, SimoneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sikic, DanijelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Denzinger, StefanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Burger, MaximilianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hartmann, ArndtUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Otto, WolfgangUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-178901
DOI: 10.1016/j.clgc.2018.01.009
Journal or Publication Title: Clin. Genitourin. Cancer
Volume: 16
Number: 4
Page Range: S. 248 - 259
Date: 2018
Publisher: CIG MEDIA GROUP, LP
Place of Publication: DALLAS
ISSN: 1938-0682
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
MESSENGER-RNA EXPRESSION; CELL-CARCINOMA; PROGNOSTIC VALUE; ALLELIC LOSSES; CANCER; RECURRENCE; VALIDATION; GUIDELINES; MUTATIONS; SURVIVALMultiple languages
Oncology; Urology & NephrologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/17890

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