Universität zu Köln

Breyer, Johannes, Wirtz, Ralph M., Erben, Philipp ORCID: 0000-0002-8279-7636, Rinaldetti, Sebastien, Worst, Thomas S., Stoehr, Robert, Eckstein, Markus, Sikic, Danijel, Denzinger, Stefan, Burger, Maximilian, Hartmann, Arndt and Otto, Wolfgang (2019). FOXM1 overexpression is associated with adverse outcome and predicts response to intravesical instillation therapy in stage pT1 non-muscle-invasive bladder cancer. BJU Int., 123 (1). S. 187 - 197. HOBOKEN: WILEY. ISSN 1464-410X

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Abstract

ObjectiveTo investigate the role of forkhead box protein M1 (FOXM1) mRNA expression and its prognostic value in stage pT1 non-muscle-invasive bladder cancer (NMIBC). Patients and MethodsClinical data and formalin-fixed paraffin-embedded tissues from transurethral resection of the bladder from patients with stage pT1 NMIBC, treated with an organ-preserving approach, were analysed retrospectively. Total RNA was isolated using commercial RNA extraction kits, and mRNA expression of FOXM1, MKI67, KRT20 and KRT5 was measured by single-step quantitative RT-PCR using RNA-specific TaqMan Assays. Statistical analysis was performed using Spearman's Rho, Wilcoxon or Kruskal-Wallis tests, Kaplan-Meier estimates of recurrence-free (RFS), progression-free (PFS) and cancer-specific survival (CSS) and Cox regression analysis. ResultsData from 296 patients (79.4% men, median age 72 years) were available for the final evaluation. Spearman correlation analysis showed that mRNA expression of FOXM1 was significantly correlated with MKI67 (: 0.6530, P < 0.001) and with the luminal subtype, reflected by the positive correlation with KRT20 (: 0.2113, P < 0.001). Furthermore, there was also a strong correlation of FOXM1 expression with adverse clinical and pathological variables, such as concomitant carcinoma in situ (P = 0.05), multifocal tumours (P = 0.005) and World Health Organization 1973 grade 3 disease (P < 0.001). Kaplan-Meier analysis showed overexpression of FOMX1 to be associated with worse PFS (P = 0.028) and worse CSS (P = 0.015). FOXM1 overexpression was also shown to be a predictive risk factor for CSS (hazard ratio 1.61 [1.13-2.34], L-R chi-squared: 7.19, P = 0.007). FOXM1 overexpression identified a subgroup of patients within the luminal subtype with worse RFS (P = 0.017), PFS (P < 0.001) and CSS (P = 0.015). Patients with low FOXM1 expression had better outcomes, irrespective of instillation therapy, whereas patients with high FOXM1 expression benefitted from intravesical chemotherapy with mitomycin C. ConclusionHigh FOXM1 expression was associated with adverse clinical and pathological features and worse outcomes, and predicted response to intravesical instillation therapy in patients with stage pT1 NMIBC.

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 Rinaldetti, Sebastien UNSPECIFIED UNSPECIFIED UNSPECIFIED Worst, Thomas S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Stoehr, Robert UNSPECIFIED UNSPECIFIED UNSPECIFIED Eckstein, Markus 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:38-140270
DOI:	10.1111/bju.14525
Journal or Publication Title:	BJU Int.
Volume:	123
Number:	1
Page Range:	S. 187 - 197
Date:	2019
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1464-410X
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language UROTHELIAL CARCINOMA; TRANSCRIPTION FACTOR; MEDIATES RESISTANCE; RISK STRATIFICATION; MOLECULAR SUBTYPES; EXPRESSION; RECURRENCE; PROGRESSION; VALIDATION; GUIDELINES Multiple languages Urology & Nephrology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/14027