Skip to main content

Advertisement

Log in

Increased nucleophosmin expression is a strong predictor of recurrence and prognosis in patients with N0M0 upper tract urothelial carcinoma undergoing radical nephroureterectomy

  • Original Article
  • Published:
World Journal of Urology Aims and scope Submit manuscript

Abstract

Purpose

We aimed to evaluate whether increased nucleophosmin expression predicts recurrence and survival in upper tract urothelial carcinoma (UTUC).

Methods

Specimens from 101 patients with N0M0 UTUC undergoing radical nephroureterectomy were evaluated. Nucleophosmin expression was determined immunohistochemically and categorized into two groups according to nucleophosmin staining intensity. The association between nucleophosmin expression and various clinicopathological factors including Ki-67 expression was analyzed. Multivariate analyses were performed to identify the independent predictors of extraurothelial recurrence and cancer-specific survival.

Results

High nucleophosmin expression was significantly correlated with tumor location, pT ≥3, lymphovascular invasion, lymph node metastasis, and high Ki-67 expression. Patients whose tumors demonstrated high nucleophosmin expression had a significantly higher rate of extraurothelial recurrence and a lower survival rate than those with low nucleophosmin expression. Multivariate analysis showed that pT ≥3, lymph node metastasis, high nucleophosmin expression, and high Ki-67 expression were independent predictors of extraurothelial recurrence. When patients were stratified into three groups according to the number of risk factors, the 2-year extraurothelial recurrence-free survival rates were 92.9% in patients with 0 or 1 risk factor, 76.5% in patients with 2 risk factors, and 9.1% in patients with 3 or 4 risk factors. Regarding cancer-specific survival, lymphovascular invasion and high nucleophosmin expression were independent predictors.

Conclusions

Increased nucleophosmin expression was a strong predictor of extraurothelial recurrence and cancer-specific survival in patients with N0M0 UTUC undergoing radical nephroureterectomy. Our risk stratification models integrating nucleophosmin expression may provide valuable information on disease recurrence and prognosis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Abbreviations

CIS:

Carcinoma in situ

CSS:

Cancer-specific survival

CT:

Computed tomography

EURFS:

Extraurothelial recurrence-free survival

LVI:

Lymphovascular invasion

NPM:

Nucleophosmin

pT stage:

Pathological T stage

RNU:

Radical nephroureterectomy

UC:

Urothelial carcinoma

UTUC:

Upper tract urothelial carcinoma

References

  1. Krabbe LM, Bagrodia A, Lotan Y et al (2014) Prospective analysis of Ki-67 as an independent predictor of oncologic outcomes in patients with high grade upper tract urothelial carcinoma. J Urol 191:28–34

    Article  CAS  PubMed  Google Scholar 

  2. Margulis V, Shariat SF, Matin SF et al (2009) Outcomes of radical nephroureterectomy: a series from the upper tract urothelial carcinoma collaboration. Cancer 115(6):1224–1233

    Article  PubMed  Google Scholar 

  3. Miyazaki Y, Kosaka T, Mikami S et al (2012) The prognostic significance of vasohibin-1 expression in patients with upper urinary tract urothelial carcinoma. Clin Cancer Res 18:4145–4153

    Article  CAS  PubMed  Google Scholar 

  4. Yeh HC, Huang CH, Yang SF et al (2010) Nuclear factor-κB activation predicts an unfavourable outcome in human upper urinary tract urothelial carcinoma. BJU Int 106:1223–1229

    Article  PubMed  Google Scholar 

  5. Liang PI, Wang YH, Wu TF et al (2013) IGFBP-5 overexpression as a poor prognostic factor in patients with urothelial carcinomas of upper urinary tracts and urinary bladder. J Clin Pathol 66:573–582

    Article  CAS  PubMed  Google Scholar 

  6. Lee DJ, Xylinas E, Rieken M et al (2014) Insulin-like growth factor messenger RNA-binding protein 3 expression helps prognostication in patients with upper tract urothelial carcinoma. Eur Urol 66:379–385

    Article  CAS  PubMed  Google Scholar 

  7. Fromont G, Roupret M, Amira N et al (2005) Tissue microarray analysis of the prognostic value of E-cadherin, Ki67, p53, p27, survivin and MSH2 expression in upper urinary tract transitional cell carcinoma. Eur Urol 48:764–770

    Article  CAS  PubMed  Google Scholar 

  8. Nakanishi K, Hiroi S, Tominaga S et al (2005) Expression of hypoxia-inducible factor-1α protein predicts survival in patients with transitional cell carcinoma of the upper urinary tract. Clin Cacer Res 11:2583–2590

    Article  CAS  Google Scholar 

  9. Kosaka T, Kikuchi E, Mikami S et al (2010) Expression of Snail in upper urinary tract urothelial carcinomas: prognostic significance and implications for tumor invasion. Clin Cancer Res 16:5814–5823

    Article  CAS  PubMed  Google Scholar 

  10. Jeon HG, Jeong IG, Bae J et al (2010) Expression of Ki-67 and Cox-2 in patients with upper urinary tract urothelial carcinoma. Urology 76:513.e7–513.e12

    Google Scholar 

  11. Chen CL, Tsui KH, Lin CY et al (2007) Can probability of genetic mutation be an indicator of clinical relevance? Genomics 90:746–750

    Article  CAS  PubMed  Google Scholar 

  12. Lindstrom MS (2011) NPM1/B23: a multifunctional chaperone in ribosome biogenesis and chromatin remodeling. Biochem Res Int 2011:195209

    Article  PubMed  Google Scholar 

  13. Yang YF, Zhang XY, Yang M et al (2014) Prognostic role of nucleophosmin in colorectal carcinomas. Asian Pac J Cancer Prev 15:2021–2026

    Article  PubMed  Google Scholar 

  14. Li Y, Sun Z, Liu K et al (2014) Prognostic significance of the co-expression of nucleophosmin and trefoil factor 3 in postoperative gastric cancer patients. Mol Clin Oncol 2:1055–1061

    PubMed  PubMed Central  Google Scholar 

  15. Londero AP, Orsaria M, Tell G et al (2014) Expression and prognostic significance of APE/Ref and NPM1 proteins in high-grade ovarian serous cancer. Am J Pathol 141:404–414

    Google Scholar 

  16. Tsui KH, Juang HH, Lee TH et al (2008) Association of nucleophosmin/B23 with bladder cancer recurrence based on immunohistochemical assessment in clinical samples. Acta Pharmacol Sin 29:364–370

    Article  CAS  PubMed  Google Scholar 

  17. Hamada S, Horiguchi A, Asano T et al (2014) Prognostic impact of fatty acid synthase expression in upper urinary tract urothelial carcinoma. Jpn J Clin Oncol 44(5):486–492

    Article  PubMed  Google Scholar 

  18. Yeh CW, Huang SS, Lee RP et al (2006) Ras-dependent recruitment of c-Myc for transcriptional activation of nucleophosmin/B23 in highly malignant U1 bladder cancer cells. Mol Pharmacol 70:1443–1453

    Article  CAS  PubMed  Google Scholar 

  19. Yung BY (2007) Oncogenic role of nucleophosmin/B23. Chang Gung Med J 30:285–292

    PubMed  Google Scholar 

  20. Dhar SK, Lynn BC, Daosukho C et al (2004) Identification of nucleophosmin as an NF-kappaB co-activator for the induction of the human SOD2 gene. J Biol Chem 279:28209–28219

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Kamarajugadda S, Cai Q, Chen H et al (2013) Manganese superoxide dismutase promotes anoikis resistance and tumor metastasis. Cell Death Dis 4:e504

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Tsui KH, Cheng AJ, Chang PL et al (2004) Association of nucleophosmin/B23 mRNA expression with clinical outcome in patients with bladder carcinoma. Urology 64:839–844

    Article  PubMed  Google Scholar 

  23. Booth DG, Takagi M, Sanchez-Pulido L et al (2014) Ki-67 is a PP1-interacting protein that organizes the mitotic chromosome periphery. Elife 3:e01641

    PubMed  PubMed Central  Google Scholar 

Download references

Authors’ contribution

HS was involved in study concept and design, data collection, statistical analysis, interpretation of data, and drafting of the manuscript. KI was involved in study concept and design, data collection, statistical analysis, interpretation of data, and critical revision of the manuscript for important intellectual content. TA was involved in interpretation of data and critical revision of the manuscript. KK was involved in data collection and critical revision of the manuscript. AS was involved in interpretation of data and critical revision of the manuscript. JA was involved in data collection, interpretation of data, and critical revision of the manuscript. AH was involved in data collection, interpretation of data, and critical revision of the manuscript. KS was involved in data collection and critical revision of the manuscript. TA was involved in study concept and design, interpretation of data, critical revision of the manuscript for important intellectual content, and supervision.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Harutake Sawazaki.

Ethics declarations

Conflict of interest

None.

Informed consent

No informed consent was obtained from human participants, since all data were anonymous.

Ethical standards

This study has been approved by the appropriate ethics committee.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sawazaki, H., Ito, K., Asano, T. et al. Increased nucleophosmin expression is a strong predictor of recurrence and prognosis in patients with N0M0 upper tract urothelial carcinoma undergoing radical nephroureterectomy. World J Urol 35, 1081–1088 (2017). https://doi.org/10.1007/s00345-016-1977-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00345-016-1977-1

Keywords

Navigation