FOXM1 overexpression is associated with adverse outcome and predicts response to intravesical instillation therapy in stage pT1 non-muscle-invasive bladder cancer
Objective: To 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 Methods; Clinical data and formalin-fixed paraffin-embedded tissues from transurethral resection of the bladder from pa...
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| Main Authors: | , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
2019
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| In: |
BJU international
Year: 2018, Volume: 123, Issue: 1, Pages: 187-196 |
| ISSN: | 1464-410X |
| DOI: | 10.1111/bju.14525 |
| Online Access: | Verlag, Volltext: https://doi.org/10.1111/bju.14525 Verlag, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1111/bju.14525 
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| Author Notes: | Johannes Breyer, Ralph M. Wirtz, Philipp Erben, Sebastien Rinaldetti, Thomas S. Worst, Robert Stoehr, Markus Eckstein, Danijel Sikic, Stefan Denzinger, Maximilian Burger, Arndt Hartmann and Wolfgang Otto |
| Summary: | Objective: To 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 Methods; Clinical 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. Results: Data 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 (ρ: 0.6530, P < 0.001) and with the luminal subtype, reflected by the positive correlation with KRT20 (ρ: 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. Conclusion: High 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. |
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| Item Description: | First published: 18 August 2018 Gesehen am 15.08.2019 |
| Physical Description: | Online Resource |
| ISSN: | 1464-410X |
| DOI: | 10.1111/bju.14525 |