Is Overexpression of Ki-67 a Prognostic Biomarker of Upper Tract Urinary Carcinoma? A Retrospective Cohort Study and Meta-Analysis

Abstract

Background: Upper tract urinary carcinoma (UTUC) is a relatively uncommon but aggressive disease. The Ki-67 antigen is a classic marker of cellular proliferation, but there is still controversy regarding the significance and importance of Ki-67 in tumor progression. Methods: In this study, we first detected Ki-67 expression in UTUC patients by immunohistochemistry (IHC). Subsequently, we quantitatively combined the results with those from the published literature in a meta-analysis after searching several databases. Results: IHC results demonstrated that patients with muscle-invasive tumors (T2-T4) had higher Ki-67 expression than those with non-muscle-invasive tumors (Tis-T1), suggesting that high Ki-67 expression may be associated with the aggressive form of UTUC. Kaplan-Meier curves showed that patients with high Ki-67 expression had significantly poorer cancer-specific survival (CSS) and disease-free survival (DFS). Furthermore, multivariate analysis suggested that Ki-67 expression was an independent prognostic factor for CSS (hazard ratio, HR=3.196) and DFS (HR=3.517) in UTUC patients. Then, a meta-analysis of the published literature investigating Ki-67 expression and its effects on UTUC prognosis was conducted. After searching the PubMed, Medline, Embase, Cochrane Library and Scopus databases, 12 articles met the eligibility criteria for this analysis. The B. Fan and H. Zhang contributed equally to this work.

Significance of p53, p27, Ki-67, E-cadherin, and HER2 expression in upper urinary tract urothelial carcinoma

“…Ki-67 expression has been reported previously in 53 to 88% of UTUC [8,10,11,26,27]. In our study, we observed positive Ki-67 expression in 69.7% of cases.…”

“…The immunostaining was assessed semi-quantitatively by considering the percentage of positive cells and staining intensity as described previously [8,18]. Ki-67 expression was classified as low (≤ 20% of cell nuclei stained positive for Ki-67), high (> 20%), and negative (0%) [10].…”

“…In bladder cancer, Ki-67 was linked to tumor stage, grade, and recurrence [9]. By contrast, in UTUC, the Ki-67 significance remains controversial [8,10,11]. E-cadherin is a transmembrane glycoprotein implicated in tissue integrity.…”

The predictive value of preoperative positive urine cytology for development of bladder cancer after nephroureterectomy in patients with upper urinary tract urothelial carcinoma: A retrospective multi-center case-control study and meta-analysis

“…Univariate data will be adopted when the available results emerge. (2) If HRs and their variance were not reported, we performed a calculation from the survival comparison statistics and its variance, which has less reliability than direct data [50][51][52]. In addition, because of the differences in the diagnostic criteria for urinary cytology among different countries and regions, the quality of this study would have been improved by standardized protocols.…”

Aspirin use is not associated with the risk or prognosis of bladder cancer: a case‐control study and meta-analytic assessment

“…Some included studies did not provide available values of HR, RR or OR from multivariate analysis, so we performed calculations from the univariate data and compared them through formula calculations. The statistical methods we used cannot replace all the research methods, and the conclusions we obtained without correlation are limited to the scope of our research, which may have some statistical errors [63,64]. Second, we only focused on researching patients who regularly consumed aspirin.…”