The Prognostic Role of Ki-67/MIB-1 in Cervical Cancer: A Systematic Review with Meta-Analysis

BACKGROUND A significant relationship has been reported in which Ki-67/MIB-1 expression is correlated with survival in cervical cancer patients. However, the prognostic value of Ki-67/MIB-1 in cervical cancer is still not well understood. MATERIAL AND METHOD A meta-analysis was carried out to explore the prognostic value of Ki-67/MIB-1 on overall survival (OS) and/or disease-free survival (DFS) in cervical cancer. The databases of PubMed, ISI Web of Science, EMBASE, Cochrane Central Register of Controlled Trials, ScienceDirect, and Wiley Online Library were used to identify relevant literature. RESULTS We included 18 studies covering 1344 patients in the meta-analysis. The effect of Ki-67/MIB-1 on OS for pooled random effects HR estimate was 1.63 (95% confidence intervals (CI) 1.09-2.45; P<0.05). Subgroup analysis by ethnicity suggested that high expression of Ki-67/MIB-1 had association with Asians (1.84, 95% CI 1.04-3.23), but not with Africans (HR=1.53, 95% CI 0.34-6.86) or Europeans (HR=1.29, 95% CI 0.74-2.23). Furthermore, subgroup analysis of diverse treatments revealed no difference in surgery (HR=1.97, 95% CI 0.78-4.99) and radiation therapy (RT) (HR=1.56, 95% CI 0.93-2.63). The pooled HR for DFS was 1.26 (95% CI 0.58-2.73; P>0.05) and the subgroup analysis indicated Ki-67/MIB1 was associated with DFS (HR=3.67, 95% CI 2.65-5.09) in Asians. In the treatment subgroup analysis, no direct value was found among surgery (HR=1.13, 95% CI 0.10-13.53) and RT (HR=1.26, 95% CI 0.71-2.24). CONCLUSIONS Our meta-analysis concludes that Ki-67/MIB-1 had a prognostic value for OS in cervical cancer patients. To further evaluate the prognostic role of Ki-67/MIB-1 on DFS, studies with larger numbers of patients are needed to validate our findings.