MyD88基因突变在弥漫大B细胞淋巴瘤中的临床意义

Clinical significance of MyD88 gene mutation in diffuse large B-cell lymphoma

目的探讨弥漫大B细胞淋巴瘤(DLBCL)患者中MyD88基因的突变情况及与临床病理特征和预后的关系。方法收集131例初诊DLBCL的临床病理资料,石蜡包埋病理组织采用二代测序法检测DLBCL患者MyD88基因突变状况,根据该基因的突变状态分为MyD88突变组和野生组,分析两组患者的临床病理特征及生存情况,并探讨影响DLBCL患者预后的因素。结果131例DLBCL患者中,MyD88突变患者31例(23.7%),其中L265P位点突变率最高,为58.1%(18/31)。MyD88基因突变状态与患者性别、年龄、Ann Arbor分期、Hans分型、IPI评分及MYC/Bcl-2双表达均无关(P>0.05);但MyD88突变与患者的疾病累及部位明显相关,原发结外DLBCL患者的MyD88突变率为36.7%(18/49),明显高于原发结内病变患者的15.9%(13/82),差异有统计学意义(P=0.025)。此外,MyD88基因突变与肿瘤细胞增殖指数Ki-67蛋白表达密切相关(P=0.027)。MyD88基因突变组和野生组的2年生存率分别为78.0%和75.2%,2年无进展生存率分别为62.5%和52.0%,以上差异均无统计学意义(P>0.05)。Cox多因素分析显示,Ann Arbor分期、MYC/Bcl-2是否双表达是影响患者无进展生存期的独立预后因素。结论有结外病变的DLBCL患者中存在较高的MyD88基因突变率,该基因突变与肿瘤细胞的增殖指数密切相关,但MyD88突变不影响患者的长期生存。

Objective To analyze the mutation of MyD88 gene in patients with diffuse large B-cell lymphoma(DLBCL)and investigate the relationship between MyD88 gene mutation and clinicopathological characteristics and prognosis of DLBCL patients.Methods The clinicopathological features of 131 cases of DLBCL were collected retrospectively,and the MyD88 mutation of DLBCL were detected by next-generation sequencing.According to the mutation status of the gene,DLBCL patients were divided into MyD88 mutation group and wild group,and the relationship between MyD88 gene mutation with the clinicopathological characteristics and prognosis of DLBCL were analyzed.Results Among 131 DLBCL patients,31 patients with MyD88 mutation(23.7%),of which the L265P site mutation rate was the highest(18/31,58.1%).The mutation status of MyD88 gene was not associated with gender,age,Ann Arbor stage,Hans type,IPI score and MYC/Bcl-2 protein double expression(P>0.05).The mutation rate of MyD88 was 36.7%in 49 patients with primary extranodal DLBCL,which was significantly higher than that of 15.9%(13/82)of patients with primary intranodal lesions(P=0.025).MyD88 gene mutation was closely related to the protein expression of tumor cell proliferation index Ki-67(P=0.027).The 2-year survival rate of MyD88 mutation group and wild group was 78.0%and 75.2%,and the 2-year progression free survival rate was 62.5%and 52.0%,but all the data had no statistical difference(P>0.05).Cox multivariate analysis showed that Ann Arbor stage and MYC/Bcl-2 double expression were independent prognostic factors of progression free survival.Conclusion There is a higher MyD88 gene mutation rate in DLBCL patients with extranodal disease.The MyD88 gene mutation is closely related to the proliferation index of tumor cells,but the mutation does not affect the patient's long-term survival.