The prognostic role of Ki-67/MIB-1 in meningioma A systematic review with meta-analysis

Background: Ki-67 is a typical immunohistochemical marker for cell proliferation. Higher expression of Ki-67 is correlated with poor clinical outcomes in several cancers. However, the prognostic value of Ki-67 on the prognosis of meningiomas is still controversial. The purpose of this meta-analysis was to evaluate the prognostic value of Ki-67 in meningiomas. Methods and materials: We searched Medline and EMBASE from inception to December 31, 2018, to identify relevant articles. Using a fixed or random effects model, pooled hazard ratios (HRs) for overall survival (OS) and disease/progression/recurrence-free survival (D/P/RFS) were estimated. Results: A total of 43 studies, comprising 5012 patients, were included in this analysis. Higher Ki-67 expression levels were significantly associated with worse OS (HR= 1.565; 95% CI: 1.217-2.013) and D/P/RFS (HR= 2.644; 95% CI: 2.264-3.087) in meningiomas. Subgroup analysis revealed that all the included factors (ethnicity, tumor grade, HR sources, definition of cutoffs, cutoff values) for heterogeneity investigation can affect the pooled results. Among them, the definitions of cutoffs and cutoff values factor are the two main contributors toward heterogeneity. Multivariable meta-regression analysis also showed that methodologies used for cutoff value definition contributed to the high inner-study heterogeneity. Conclusions: Higher Ki-67 expression levels negatively influenced survival in meningiomas. A higher cutoff value (>4%) is more appropriate for prognosis prediction. It is highly recommended that Ki-67 expression profile could be assessed in meningiomas treatment for predicting survival. And patients with elevated expression of Ki-67 need to have close follow-ups.