title: 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 eligible studies included a total of 1740 patients with a mean number of 82 patients per study (range, 38-475). The combined results showed that increased Ki-67 levels were associated with poor survival and disease progression, with a pooled HR estimate of 2.081 and 2.791, respectively. In subgroup analysis, the pooled HR was statistically significant for cancer-specific survival (HR=2.276), metastasis-free survival (HR=3.008) and disease-free survival (HR=6.336).
  
  
  CONCLUSIONS
  In conclusion, high Ki-67 expression was associated with poor survival in patients with UTUC, as well as a high risk of disease progression, although these findings need to be interpreted with caution. Large-scale, adequately designed, prospective trials are needed to further confirm the value of Ki-67 in prognosis of UTUC patients.
authors.affiliation: Graduate School, Dalian Medical University, Dalian, Liaoning, P.R. China.
authors.forename: Bo
authors.initials: B
authors.lastname: Fan
authors.forename: Hongshuo
authors.initials: H
authors.lastname: Zhang
authors.forename: Huidan
authors.initials: H
authors.lastname: Jin
authors.forename: Yu
authors.initials: Y
authors.lastname: Gai
authors.forename: Honglong
authors.initials: H
authors.lastname: Wang
authors.forename: Huafeng
authors.initials: H
authors.lastname: Zong
authors.forename: Mingyu
authors.initials: M
authors.lastname: Jin
authors.forename: Hao
authors.initials: H
authors.lastname: Yang
authors.forename: Shuping
authors.initials: S
authors.lastname: Wan
authors.forename: Jiabin
authors.initials: J
authors.lastname: Zhu
authors.forename: Siyao
authors.initials: S
authors.lastname: Xu
authors.forename: Jianbo
authors.initials: J
authors.lastname: Wang
authors.forename: Deyong
authors.initials: D
authors.lastname: Yang
authors.forename: Xishuang
authors.initials: X
authors.lastname: Song
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D019394:Ki-67 Antigen / Q000378:metabolism*; D008297:Male; D015999:Multivariate Analysis; D011379:Prognosis; D012189:Retrospective Studies; D014571:Urologic Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen