Abstract
Previous studies have elevated the prognostic value of Ki-67 in renal cell carcinoma (RCC), but the reports are controversial and inconsistent. We conducted a systematic review and meta-analysis to clarify the significance of Ki-67 in RCC prognosis. We systematically searched PubMed, Web of Science, and Embase to identify relevant studies until April 2016. Based on the inclusion and exclusion criteria, 20 studies, including 5,398 patients, were eligible for further analysis. Results showed that high Ki-67 expression in RCC was associated with poor OS (HR = 1.95, 95% CI: 1.44–2.64), CSS (HR = 1.67, 95% CI: 1.47–1.89), and DFS (HR = 2.56, 95% CI: 1.79–3.67). In addition, high Ki-67 expression was significantly associated with TNM stage (III/IV vs. I/II: RR = 2.03, 95% CI: 1.68–2.44), pathological T stage (T3/T4 vs. T1/T2: RR = 1.67, 95% CI: 1.35–2.06), metastasis (yes vs. no: RR = 2.15, 95% CI: 1.77–2.62), and Fuhrman grade (III/IV vs. I/II: RR = 1.77, 95% CI: 1.20–2.60). Our study suggested that Ki-67 was a prognostic marker in RCC. High Ki-67 expression was correlated with poor prognosis and advanced clinicopathological features, and it could serve as a biomarker for disease management.
Highlights
Ki-67, a proliferation marker that is expressed during the cell cycles of G1, S, G2, and M stages, except G0, is usually detected by immunohistochemical (IHC) staining[6]
Our meta-analysis demonstrated that high Ki-67 expression in Renal cell carcinoma (RCC) was associated with poor overall survival (OS), cancer-specific survival (CSS), and disease-free survival (DFS)
First described in 1991 by Gerdes et al.[32], Ki-67, a nuclear protein, is a famous marker of cell proliferation. It is expressed throughout the cell cycle in proliferating but not quiescent (G0) cells, so it has been used as a proliferation marker in many cancers
Summary
Ki-67, a proliferation marker that is expressed during the cell cycles of G1, S, G2, and M stages, except G0, is usually detected by immunohistochemical (IHC) staining[6]. Its strict association with cell proliferation and its co-expression with other well-known markers of proliferation indicate a pivotal role in cell division. Several studies recently reported that Ki-67 expression is associated with poor prognosis in several types of cancer[7,8,9,10]. Ki-67 was considered an unfavorable prognostic marker in RCC in many studies[11,12,13,14], but some studies reported that Ki-67 expression is prognostically irrelevant in RCC patients[15,16]. To obtain a more precise evaluation of the prognostic and clinicopathological value of Ki-67 expression in RCC, we performed a systematic review and meta-analysis to evaluate the prognostic value of Ki-67 quantitatively and explore the associations of Ki-67 with the clinicopathological features of RCC
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