title: Increased nucleophosmin expression is a strong predictor of recurrence and prognosis in patients with N0M0 upper tract urothelial carcinoma undergoing radical nephroureterectomy.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Urology, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan. harutake_sawazaki@tokyo-hmt.jp.
authors.forename: Harutake
authors.initials: H
authors.lastname: Sawazaki
authors.affiliation: Department of Urology, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Ito
authors.affiliation: Department of Urology, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan.
authors.forename: Takako
authors.initials: T
authors.lastname: Asano
authors.affiliation: Department of Urology, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Kuroda
authors.affiliation: Department of Urology, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan.
authors.forename: Akinori
authors.initials: A
authors.lastname: Sato
authors.affiliation: Department of Urology, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Asakuma
authors.affiliation: Department of Urology, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan.
authors.forename: Akio
authors.initials: A
authors.lastname: Horiguchi
authors.affiliation: Department of Urology, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Seguchi
authors.affiliation: Department of Urology, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan.
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Asano
mesh_terms: D000368:Aged; D002277:Carcinoma / Q000175:diagnosis / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007564:Japan / Q000453:epidemiology; D007668:Kidney / Q000473:pathology; D007680:Kidney Neoplasms / Q000175:diagnosis / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D000074682:Nephroureterectomy / Q000379:methods / Q000706:statistics & numerical data; D009687:Nuclear Proteins / Q000378:metabolism*; D000090243:Nucleophosmin; D011379:Prognosis; D012008:Recurrence; D012189:Retrospective Studies; D018570:Risk Assessment / Q000379:methods; D015996:Survival Rate; D014513:Ureter / Q000473:pathology; D014516:Ureteral Neoplasms / Q000175:diagnosis / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D019459:Urothelium / Q000473:pathology*
chemical_list: C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D000090243:Nucleophosmin
keywords: Nucleophosmin; Prognosis; Recurrence; Upper tract urothelial carcinoma