c-Myc、Bcl-2和Bcl-6蛋白表达对原发中枢神经系统淋巴瘤的治疗选择和预后影响

Effect of c-Myc,Bcl-2 and Bcl-6 Protein Expression on Treatment Selection and Prognosis of Primary Central Nervous System Lymphoma

目的探讨c-Myc、Bcl-2和Bcl-6蛋白表达对原发中枢神经系统淋巴瘤(primary central nervous system lymphoma,PCNSL)的预后影响及在治疗方案选择上的指导意义。方法回顾性分析56例PCNSL患者的临床资料,对其病理组织进行免疫组织化学染色(IHC)检测c-Myc、Bcl-2、Bcl-6、CD20、CD10及Mum-1,采用Kaplan-Meier法和COX多因素回归模型进行生存及预后分析,分析上述蛋白表达与预后及治疗方案选择的关系。结果56例PCNSL患者中位总生存时间(OS)25个月,2年生存率为50.0%。COX多因素分析发现,Bcl-2蛋白阳性、c-Myc/Bcl-2蛋白双表达及未予HD-MTX治疗是影响PCNSL患者OS的独立不良预后因素。在予HD-MTX治疗的患者中,c-Myc/Bcl-2蛋白双表达和非双表达患者总体反应率(ORR)分别为42.1%和73.3%,差异有统计学意义(P=0.029)。联用布鲁顿酪氨酸激酶(BTK)抑制剂患者中,非生发中心型(non-GCB)患者的ORR明显高于生发中心型(GCB型)(77.8%vs 16.7%,P=0.041)。结论Bcl-2蛋白阳性表达、c-Myc/Bcl-2蛋白双表达是影响PCNSL患者预后的独立危险因素。HD-MTX为基础的联合化疗可明显延长PCNSL患者生存期,联合BTK抑制剂用于non-GCB型患者可获得较好的ORR。

Objective To explore the prognostic value of c-Myc,Bcl-2,Bcl-6 protein expression and the significance of guiding the treatment selection on primary central nervous system lymphoma(PCNSL).Methods A total of 56 cases that diagnosed PCNSL were retrospectively analyzed by retrieving clinical data.The expression of c-Myc,Bcl-2,Bcl-6,CD20,CD10 and Mum-1 were redetected by immunohistochemical staining(IHC).The adverse prognostic factors were analyzed by Kaplan-Meier and COX multivariate regression model.And analyze the relationship between the above protein expression with prognosis and efficacy.Results The median overall survival time(OS)of 56 PCNSL patients was 25 months,and the 2-year overall survival rates was 50.0%.COX multivariate analysis showed that Bcl-2 protein positive,co-expression of c-Myc and Bcl-2,and without HD-MTX treatment were independent poor prognostic factors affecting OS in PCNSL patients.Among the patients treated with HD-MTX,the overall response rate(ORR)of c-Myc/Bcl-2 double expression and non-double expression were 42.1%and 73.3%respectively,the difference were statistically significant(P=0.029).In patients treated with bruton tyrosine kinase(BTK)inhibitor,the ORR of patients with non-germinal center B-cell(non-GCB)type was significantly higher than that of germinal center B-cell(GCB)type(77.8%vs 16.7%,P=0.041).Conclusion Bcl-2 protein positive expression and c-Myc/Bcl-2 protein co-expression are independent risk factors influencing the prognosis in PCNSL patients.HD-MTX-based chemotherapy significantly prolong the survival of PCNSL patients,and the combination of BTK inhibitor for patients with non-GCB type can achieve better ORR.