Backgrounds Urothelial carcinoma of the urinary bladder (UCUB) is prevalent in developed countries. It often shows genetic instability and is associated with amplification (or gain) of various oncogenic genes or suppressive genes. Rsf-1, a subunit of ATP-dependent chromatin-remodelling complexes that mediates ATPase-dependent chromatin remodelling, confers tumour aggressiveness in certain carcinomas. The authors evaluate the Rsf-1 gene and expression status and its associations with clinicopathological features and survival in their UCUB collection.
Methods Immunohistochemistry was used to assess the Rsf-1 expression profile in 295 UCUB specimens, and was found to correlate with clinicopathological data. Real-time RT-PCR and fluorescence in situ hybridisation were used to detect RSF-1 mRNA expression and gene dosage in 20 independent cases. Western blot analysis was used to evaluate Rsf-1 protein expression in human urothelial cell lines.
Results Rsf-1 overexpression was demonstrated in 101 cases (34.2%), and was significantly associated with advanced primary tumour (p<0.001), nodal metastasis (p=0.004), higher histological grades (p=0.001) and frequent mitoses (p<0.001). Moreover, it was predictive in disease-specific survival and metastasis-free survival in both univariate and multivariate analyses (p<0.0001 for both). Although RSF-1 gene amplification can be barely detected, its mRNA expression is significantly enhanced in tumours with higher primary tumour (p=0.041) and positive nodal statuses (p=0.010), respectively. Rsf-1 protein was abundant in invasive urothelial carcinoma cells but was not benign.
Conclusions Overexpression of Rsf-1 is associated with higher tumour stage and poorer clinical outcome. The current study by the authors suggests gene amplification-independent mechanisms driving Rsf-1 overexpression during UCUB tumour progression.
- urinary bladder
- urothelial carcinoma
- molecular pathology
- tumour biology
- molecular oncology
- molecular genetics
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Funding This work was supported in part by grants from the Chi-Mei Medical Center (CMFHR10044) and the Department of Health, Taiwan (DOH99-TD-C-111-004). The authors are grateful to the Translational Research Laboratory of Human Cancers of Chi-Mei Medical Center for providing critical technical assistance.
Competing interests None.
Ethics approval Ethics approval was provided by the Institutional Review Board of Chi-Mei Medical Center (IRB10102-004) approved immunohistochemical, FISH and qRT-PCR study by using human samples.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement The original immunostaining and statistical data are available from the corresponding author.