Breyer, Johannes and Wirtz, Ralph M. and Erben, Philipp and Rinaldetti, Sebastien and Worst, Thomas S. and Stoehr, Robert and Eckstein, Markus and Sikic, Danijel and Denzinger, Stefan and Burger, Maximilian and 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 INTERNATIONAL, 123 (1). pp. 187-196. ISSN 1464-4096, 1464-410X
Full text not available from this repository. (Request a copy)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: | Article |
|---|---|
| Uncontrolled Keywords: | UROTHELIAL CARCINOMA; TRANSCRIPTION FACTOR; MEDIATES RESISTANCE; RISK STRATIFICATION; MOLECULAR SUBTYPES; EXPRESSION; RECURRENCE; PROGRESSION; VALIDATION; GUIDELINES; FOXM1; non-muscle-invasive bladder cancer; pT1; prognosis; instillation therapy |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Urologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 22 Apr 2020 07:46 |
| Last Modified: | 22 Apr 2020 07:46 |
| URI: | https://pred.uni-regensburg.de/id/eprint/27920 |
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