MYC, BCL2, and BCL6 expression as prognostic indicators in primary central nervous system lymphoma: A systematic review and meta-analysis

We conducted a meta-analysis to comprehensively assess the predictive role of MYC, BCL2, and BCL6 genetic alterations and protein expression in PCNSL for clinical application. A systematic retrieval was performed on PubMed, Embase, the Cochrane library, Web of Science, Scopus, and 2 Chinese databases. Cohort studies discussing the prognostic impact of MYC, BCl2, or BCL6 genetic alterations or gene expression in PCNSL were selected. The pooled hazard ratio (HR) and median survival ratio (MSR) were calculated. 31 studies involving 1739 patients fulfilled our inclusion criteria. MYC expression was significantly associated with short median OS (MSR = 0.62; 95%CI, 0.44–0.88) and PFS (HR = 1.53; 95%CI, 1.06–2.20). No significant association was found between BCL2 expression and OS or PFS (P > 0.05). BCL6 protein positivity was significantly associated with extended median OS (MSR = 1.62; 95%CI, 1.10–2.40). MYC and BCL2 coexpression was significantly associated with short median OS (MSR = 0.61; 95%CI, 0.45–0.84). Subgroup analysis demonstrated that MYC protein positivity remained as a significant indicator for short median OS in studies whose sample size ≥ 45, treatment without WBRT, quality scale score ≥ 7, and positivity threshold set at 40% stratum (MSR < 1 and P < 0.05), but failed to reach a statistically significant difference in the other stratum. MYC expression predicts inferior median OS and PFS in PCNSL. BCL6 protein positivity is associated with a favorable prognosis. The sample size, average age of subjects, WBRT treatment, study quality, and cut-off values for discriminating positive and negative protein expression in IHC may be origins of heterogeneity.