Article Text

other Versions

PDF
Rsf-1/HBXAP overexpression is independent of gene amplification and is associated with poor outcome in patients with urinary bladder urothelial carcinoma
  1. Peir-In Liang1,
  2. Li-Ching Wu2,
  3. Jim Jinn-Chyuan Sheu3,4,
  4. Ting-Feng Wu5,
  5. Kun-Hung Shen6,
  6. Yu-Hui Wang7,
  7. Wen-Ren Wu8,
  8. Yow-Ling Shiue8,
  9. Hsuan-Ying Huang9,
  10. Han-Ping Hsu10,
  11. Yi-Hsien Chen11,
  12. Li-Tzon Chen12,
  13. Chien-Feng Li2,5,8,12,
  14. Alex C Liao6,13
  1. 1Department of Pathology, Chi-Mei Foundation Medical Center, Liouying, Tainan, Taiwan
  2. 2Department of Pathology, Chi-Mei Foundation Medical Center, Tainan, Taiwan
  3. 3Human Genetic Center, China Medical University Hospital, Taichung, Taiwan
  4. 4School of Chinese Medicine, China Medical University, Taichung, Taiwan
  5. 5Department of Biotechnology, Southern Taiwan University, Tainan, Taiwan
  6. 6Department of Urology, Chi-Mei Foundation Medical Center, Tainan, Taiwan
  7. 7Institute of Biosignal Transduction, National Cheng Kung University, Tainan, Taiwan
  8. 8Institute of Biomedical Science, National Sun Yat-Sen University, Kaohsiung, Taiwan
  9. 9Department of Pathology, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan
  10. 10College of Medicine, China Medical University, Taichung, Taiwan
  11. 11Department of Emergency Medicine, Chi-Mei Foundation Medical Center, Tainan, Taiwan
  12. 12National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan
  13. 13Department of Senior Citizen Service Management, Chia Nan University of Pharmacy and Science, Tainan, Taiwan
  1. Correspondence to Dr Alex C Liao, Department of Urology, Chi-Mei Foundation Medical Center, Tainan 710, Taiwan; chien-feng-li{at}hotmail.com

Abstract

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.

  • Rsf-1
  • urinary bladder
  • urothelial carcinoma
  • histopathology
  • molecular pathology
  • tumour biology
  • cancer
  • oncogenes
  • molecular oncology
  • molecular genetics

Statistics from Altmetric.com

Footnotes

  • 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.

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.