title: Prospective analysis of Ki-67 as an independent predictor of oncologic outcomes in patients with high grade upper tract urothelial carcinoma.
abstract: OBJECTIVE
  We determined the association of the proliferation marker Ki-67 with pathological parameters and oncologic outcomes in patients with high grade upper tract urothelial carcinoma.
  
  
  METHODS
  Immunohistochemical staining for Ki-67 was done prospectively in 101 consecutive patients undergoing radical nephroureterectomy/ureterectomy for high grade upper tract urothelial carcinoma. Data were compared based on Ki-67 status (normal vs over expressed). Survival was assessed by the Kaplan-Meier method. Cox regression analysis was done to identify independent predictors of time dependent outcomes.
  
  
  RESULTS
  Median patient age was 70.0 years and median followup was 22.0 months (range 1 to 77). Overall, 30.2% of the population experienced recurrence and 24.8% died of upper tract urothelial carcinoma. Organ confined disease (T2 or less and lymph node negative), lymphovascular invasion and sessile architecture were present in 56.3%, 33.3% and 20.8% of patients, respectively. Ki-67 was over expressed in 73.3% of patients and associated with adverse pathological features. Patients with over expressed Ki-67 had significantly worse recurrence-free survival (43.2 vs 69.0 months, p = 0.006) and cancer specific survival (48.9 vs 68.9 months, p = 0.031) than patients with normal Ki-67. Patients with nonmetastatic disease similarly had worse recurrence-free survival (40.7 vs 71.8 months, p = 0.003) and cancer specific survival (41 months vs not attained, p = 0.008) for over expressed vs normal Ki-67. After adjusting for the effects of organ vs nonorgan confined disease Ki-67 over expression was an independent predictor of recurrence-free survival in the total cohort (HR 4.3, p = 0.05) and in patients with nonmetastatic disease (HR 8.5, p = 0.038).
  
  
  CONCLUSIONS
  Ki-67 over expression was associated with adverse pathological features in cases of upper tract urothelial carcinoma. It was also an independent predictor of recurrence-free survival in patients with high grade upper tract urothelial carcinoma.
authors.affiliation: Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas; Department of Urology, University of Muenster Medical Center, Muenster, Germany.
authors.forename: Laura-Maria
authors.initials: LM
authors.lastname: Krabbe
authors.affiliation: Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas.
authors.forename: Aditya
authors.initials: A
authors.lastname: Bagrodia
authors.affiliation: Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas.
authors.forename: Yair
authors.initials: Y
authors.lastname: Lotan
authors.affiliation: Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas.
authors.forename: Bishoy A
authors.initials: BA
authors.lastname: Gayed
authors.affiliation: Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas.
authors.forename: Oussama M
authors.initials: OM
authors.lastname: Darwish
authors.affiliation: Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas.
authors.forename: Ramy F
authors.initials: RF
authors.lastname: Youssef
authors.affiliation: Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas.
authors.forename: George
authors.initials: G
authors.lastname: John
authors.affiliation: Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas.
authors.forename: Brian
authors.initials: B
authors.lastname: Harrow
authors.affiliation: Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas.
authors.forename: Corbin
authors.initials: C
authors.lastname: Jacobs
authors.affiliation: Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas.
authors.forename: Mansi
authors.initials: M
authors.lastname: Gaitonde
authors.affiliation: Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas.
authors.forename: Arthur I
authors.initials: AI
authors.lastname: Sagalowsky
authors.affiliation: Department of Urology, Medical University of Vienna, Vienna General Hospital, Vienna, Austria.
authors.forename: Shahrokh F
authors.initials: SF
authors.lastname: Shariat
authors.affiliation: Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas.
authors.forename: Payal
authors.initials: P
authors.lastname: Kapur
authors.affiliation: Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas. Electronic address: Vitaly.margulis@utsouthwestern.edu.
authors.forename: Vitaly
authors.initials: V
authors.lastname: Margulis
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D002295:Carcinoma, Transitional Cell / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000096:biosynthesis*; D007680:Kidney Neoplasms / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D014516:Ureteral Neoplasms / Q000378:metabolism*; D014571:Urologic Neoplasms / Q000378:metabolism*; D019459:Urothelium / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen
keywords: CSS; IHC; LVI; RFS; RNU; UTUC; biological markers; cancer specific survival; carcinoma; immunohistochemistry; kidney; lymphovascular invasion; radical nephroureterectomy; recurrence-free survival; upper tract urothelial carcinoma; ureter; urothelium