Low-level Ki-67 expression as an independent predictor of bladder tumour recurrence in patients with primary upper tract urothelial carcinoma after radical nephroureterectomy

Abstract

Objective: To evaluate the association of molecular markers and conventional clinicopathological factors with bladder tumour recurrence in patients with primary upper tract urothelial carcinoma after radical nephroureterectomy. Methods: The expressions of Ki-67 and P53 were measured by immunohistochemical staining prospectively in 115 consecutive patients with primary upper tract urothelial carcinoma from March 2004 to February 2014. The Cox proportional hazards regression model was used to identify independent predictors. The association between Ki-67 expression and clinicopathological variables was assessed by the χ 2 test.Results: Intravesical recurrence occurred in 13 out of 115 (11.3%) patients with a mean follow-up of 54.2 months (range: 7-130). Low-level Ki-67 expression (P = 0.010), older age (>65, P = 0.040) and lower ureter tumour (P = 0.001) were independent predictors of bladder tumour recurrence in Cox regression analysis. Ki-67 expression was elevated with the progression of tumour grade (P = 0.004) but not with stage (P = 0.186). Ki-67 overexpression was also significantly higher in aggressive pathological types (P = 0.008), but only shows an inclination towards poor oncologic outcomes in the cancer-specific survival rate (P = 0.107) and the overall survival rate (P = 0.063).Conclusions: Low-level Ki-67 expression was an independent predictor for bladder tumour recurrence, while Ki-67 overexpression was associated with adverse clinicopathological parameters and poor prognosis in patients with primary upper tract urothelial carcinoma after radical nephroureterectomy.

The Diagnostic Role of p53 and Ki 67 Immunohistochemistry in Evaluation of Urinary Bladder Carcinomas in Egyptian Patients

“…Qamar et al found that higher p53 expression can be an indicator of tumor progression and early failure of local therapy, as well as early surgical intervention, especially for superficial carcinomas. Although, the opposite results were also described by some investigators [8][9]13].…”

“…P53 is a key tumor suppressor gene involved in genomic balance, genotoxic stress response, and cell cycle apoptosis stimulation. Some studies showed correlations in urothelial bladder cancer between p53 and tumor stage and grade [7][8][9].…”

Epidermal Growth Factor Receptor and Ki-67 as Predictive Biomarkers Identify Patients Who Will Be More Sensitive to Intravesical Instillations for the Prevention of Bladder Cancer Recurrence after Radical Nephroureterectomy

“…In combination with CK20 overexpression, Ki-67 overexpression can serve as a predictor of pT1 urothelial bladder cancer recurrence [12]. Regarding UTUC, a previous study and this study show that low-level Ki-67 expression was an independent predictor of bladder tumor recurrence in patients without instillation therapy [13]. Our study also found that patients with low-level Ki-67 appeared to be more sensitive to intravesical chemotherapy; we also found that the subsequently recurring bladder tumors in patients with intravesical chemotherapy expressed more Ki-67 than those in the patients without intravesical chemotherapy.…”

“…Similar to EGFR, Ki-67 overexpression is also suggestive of high tumor grade and poor prognosis [12,13]. In combination with CK20 overexpression, Ki-67 overexpression can serve as a predictor of pT1 urothelial bladder cancer recurrence [12].…”

“…Based on previous studies, the proliferation markers Ki67 [6,7] and growth factor receptors EGFR [8,9] are two of a few biomarkers determined to have prognostic value for both bladder urothelial carcinoma and upper urinary tract urothelial carcinoma. Additionally, the expression of Ki67 and EGFR were important in predicting primary superficial bladder cancer recurrence and secondary bladder cancer after RNU [10–13]. However, though Ki67 and EGFR have the ability to predict bladder recurrence of the upper urinary tract urothelial carcinoma after RNU, the ability to predict which group of patients would be more sensitive to intravesical therapy remains unknown.…”