Universität zu Köln

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:	Creators Email ORCID ORCID Put Code Breyer, Johannes UNSPECIFIED UNSPECIFIED UNSPECIFIED Wirtz, Ralph M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Erben, Philipp UNSPECIFIED orcid.org/0000-0002-8279-7636 UNSPECIFIED Worst, Thomas S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Stoehr, Robert UNSPECIFIED UNSPECIFIED UNSPECIFIED Eckstein, Markus UNSPECIFIED UNSPECIFIED UNSPECIFIED Bertz, Simone UNSPECIFIED UNSPECIFIED UNSPECIFIED Sikic, Danijel UNSPECIFIED UNSPECIFIED UNSPECIFIED Denzinger, Stefan UNSPECIFIED UNSPECIFIED UNSPECIFIED Burger, Maximilian UNSPECIFIED UNSPECIFIED UNSPECIFIED Hartmann, Arndt UNSPECIFIED UNSPECIFIED UNSPECIFIED Otto, Wolfgang UNSPECIFIED UNSPECIFIED UNSPECIFIED
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:	Keywords Language MESSENGER-RNA EXPRESSION; CELL-CARCINOMA; PROGNOSTIC VALUE; ALLELIC LOSSES; CANCER; RECURRENCE; VALIDATION; GUIDELINES; MUTATIONS; SURVIVAL Multiple languages Oncology; Urology & Nephrology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/17890