Prospective Analysis of Ki-67 as an Independent Predictor of Oncologic Outcomes in Patients with High Grade Upper Tract Urothelial Carcinoma

• Published in: The Journal of urology Vol. 191; no. 1; pp. 28 - 34
• Main Authors: Krabbe, Laura-Maria, Bagrodia, Aditya, Lotan, Yair, Gayed, Bishoy A, Darwish, Oussama M, Youssef, Ramy F, John, George, Harrow, Brian, Jacobs, Corbin, Gaitonde, Mansi, Sagalowsky, Arthur I, Shariat, Shahrokh F, Kapur, Payal, Margulis, Vitaly
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 2014; Elsevier
• Subjects: Adult; Aged; Aged, 80 and over; Biological and medical sciences; biological markers; Biomarkers, Tumor - biosynthesis; carcinoma; Carcinoma, Transitional Cell - metabolism; Female; Humans; Immunohistochemistry; Ki-67 Antigen - biosynthesis; kidney; Kidney Neoplasms - metabolism; Male; Medical sciences; Middle Aged; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Nephrology. Urinary tract diseases; Prognosis; Tumors; Tumors of the urinary system; ureter; Ureteral Neoplasms - metabolism; Urinary tract. Prostate gland; Urologic Neoplasms - metabolism; Urology; urothelium; Urothelium - metabolism; CSS; cancer specific survival; ureter; IHC; UTUC; upper tract urothelial carcinoma; urothelium; kidney; lymphovascular invasion; carcinoma; recurrence-free survival; radical nephroureterectomy; biological markers; RNU; immunohistochemistry; LVI; RFS; Human; Nephrology; Urinary system disease; Prognosis; Biological marker; Urinary tract disease; Malignant tumor; Upper urinary tract transitional cell carcinoma; Kidney; Urology; High grade; Prospective; Urinary system; Ki67 antigen; Ureter; Predictive factor; Cancer; High malignancy; Urothelium
• ISSN: 0022-5347; 1527-3792
• DOI: 10.1016/j.juro.2013.07.012

Purpose 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. Materials and 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.