A Meta-analysis Of The Prognostic Relationship Between Ki-67Overexpression And Lymphoma And Its Various Subtypes

PurposeKi-67is a nuclear protein involved incell proliferation regulation, and its expressionhas been widely used as an index to evaluate the proliferative activity of lymphoma. However, its prognostic valuefor lymphoma is still contradictory and inconclusive.MethodsPubMed and Web of Science databases were searched with identical strategies.The impact of Ki-67expression on survival with lymphoma and various subtypes of lymphoma was evaluated through meta-analysis. The relationship between Ki-67expression and DiffuseLarge B Cell Lymphoma(DLBCL) and Mantle Cell Lymphoma(MCL)was also investigated after the introduction of a CD-20monoclonalantibody rituximab.Furthermore, we evaluated the association between Ki-67expression and the clinical-pathological features of lymphoma.ResultsA total of27studies met the inclusion criteria, which comprised3902patients. Meta-analysis suggestedthat high Ki-67expression was negatively associated with disease free survival (DFS)(HR=1.727,95%CI:1.159-2.571; P=0.007) and overall survival (OS)(HR=1.7,95%CI:1.44-2; P=0.000) for lymphoma patients.Subgroup analysis on the different subtypes of lymphoma suggested that the association between high Ki-67expressionand OS in Hodgkin Lymphoma (HR=1.511,95%CI:0.524-4.358, P=0.445) was absent, while high Ki-67expression was highly associated with worse OS for Non-Hodgkin Lymphoma(HR=1.777,95%CI:1.463-2.159, P=0.000) and its various subtypes, including NK/T lymphoma (HR=4.766,95%CI:1.917-11.849, P=0.005), DLBCL (HR=1.457,95%CI:1.123-1.891, P=0.005) and MCL (HR=2.48,95%CI:1.61-3.81, P=0.005). Furthermore, the pooled HRs for MCL was1.981(95%CI:1.099-3.569, p=0.023) with rituximab and3.123(95%CI:2.049-4.76, p=0.000) without rituximab, while for DLBCL, the combined HRs forDLBCL with and without rituximab was1.459(95%CI:1.084-2.062, p=0.014) and1.456(95%CI:0.951-2.23, p=0.084) respectively.In addition, there was no correlation between highKi-67expression and the clinical-pathological features of lymphoma including the LDH level, B symptoms, tumor stage, extranodal site, performance status and IPI score.ConclusionsThisstudyshowedthatthe prognostic significance of Ki-67expression varied in different subtypes of lymphoma andafter the introduction of rituximab.The prognostic value of Ki-67expression existed only in NHL subtypes, including DLBCL, MCL, NK/TL, but not in HL. In addition, Ki-67expression had prognostic value in DLBCL with rituximab, but the value disappeared without rituximab. However, in MCL, Ki-67expression had prognostic value both with rituximab and without rituximab. And after the introduction of rituximab, the prognostic risk in patients with high Ki-67expression decreased, which more strongly indicated the usage of rituximab in MCL patients with high Ki-67expression.This was valuable for clinical decision-making and individual prognostic evaluation.