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.
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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
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
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
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
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
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
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
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
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
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
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
Chen CL, Tsui KH, Lin CY et al (2007) Can probability of genetic mutation be an indicator of clinical relevance? Genomics 90:746–750
Lindstrom MS (2011) NPM1/B23: a multifunctional chaperone in ribosome biogenesis and chromatin remodeling. Biochem Res Int 2011:195209
Yang YF, Zhang XY, Yang M et al (2014) Prognostic role of nucleophosmin in colorectal carcinomas. Asian Pac J Cancer Prev 15:2021–2026
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
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
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
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
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
Yung BY (2007) Oncogenic role of nucleophosmin/B23. Chang Gung Med J 30:285–292
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
Kamarajugadda S, Cai Q, Chen H et al (2013) Manganese superoxide dismutase promotes anoikis resistance and tumor metastasis. Cell Death Dis 4:e504
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
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
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.
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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
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DOI: https://doi.org/10.1007/s00345-016-1977-1