中国癌症杂志 ›› 2018, Vol. 28 ›› Issue (9): 679-685.doi: 10.19401/j.cnki.1007-3639.2018.09.006

• 论著 • 上一篇    下一篇

弥漫性大B细胞淋巴瘤中MYD88基因突变及其临床病理相关性分析

于宝华,薛 田,张 岩,蒋翔男,朱晓丽,李小秋   

  1. 复旦大学附属肿瘤医院病理科,复旦大学上海医学院肿瘤学系,上海 200032
  • 出版日期:2018-09-30 发布日期:2018-10-26
  • 通信作者: 李小秋 E-mail: leexiaoqiu@hotmail.com
  • 基金资助:
    国家自然科学基金青年项目(81700195)。

MYD88 gene mutation in diffuse large B-cell lymphoma and its clinicopathological relevance

YU Baohua, XUE Tian, ZHANG Yan, JIANG Xiangnan, ZHU Xiaoli, LI Xiaoqiu   

  1. Department of Pathology, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
  • Published:2018-09-30 Online:2018-10-26
  • Contact: LI Xiaoqiu  E-mail: leexiaoqiu@hotmail.com

摘要: 背景与目的:MYD88基因在弥漫性大B细胞淋巴瘤(diffuse large B-cell lymphoma,DLBCL)中有一定突变率,但其临床病理相关性目前研究报道甚少。该研究旨在分析DLBCL中MYD88基因突变的发生率及与临床病理参数的相关性。方法:收集121例DLBCL患者的临床病理资料,采用免疫组织化学法分析其免疫表型,采用PCR扩增及直接测序法检测MYD88 L265P位点突变情况,采用统计学方法分析MYD88突变与各临床病理参数的相关性。结果:121例DLBCL患者中,38例(31.4%)检测到MYD88 L265P突变。其中男性50例,女性71例,患者性别与该基因突变没有相关性(P=0.609)。年龄≥60岁组MYD88突变率为40.3%(25/62),显著高于<60岁组(13/59,22.0%)(P=0.030)。MYD88突变主要发生在结外部位,其中最常见的是乳腺(12/13,92.3%)、男性生殖系统(10/11,90.9%)、女性生殖系统(5/6,83.3%)及中枢神经系统(4/6,66.7%);结外DLBCL中的MYD88突变率(35/98,35.7%)显著高于结内者(2/20,10%)(P=0.024)。Non-GCB型DLBCL中MYD88突变率为39.7%(25/63),显著高于GCB亚型(10/55,18.2%)(P=0.010);结外DLBCL组中MYD88突变与免疫分型的相关性更加显著(P=0.003),而结内组中两者无相关性(P=0.776)。Bcl-2蛋白阳性组(30/77,39.0%)及MYC/Bcl-2蛋白双表达组(19/46,41.3%)中MYD88突变率分别高于Bcl-2阴性组(5/40,12.5%)及非双表达组(16/70,22.9%)(P=0.003和0.034)。Ki-67增殖活性与MYD88基因突变显著相关[高增殖活性组为38.8%(33/85),低增殖活性组为6.3%(2/32)](P<0.001)。该基因突变与MYC蛋白及CD5表达均无相关性(P=0.581和0.759)。结论:MYD88 L265P突变好发于年龄≥60岁、non-GCB起源及特殊结外部位(如乳腺、中枢神经系统及生殖系统等)的DLBCL中,且具有较高增殖指数及MYC/Bcl-2蛋白双表达率;其预后相关性有待积累更多病例进一步分析。MYD88基因突变有望为揭示DLBCL发病机制及靶向治疗提供新的理论依据。

关键词: 弥漫性大B细胞淋巴瘤, MYD88基因突变, 免疫分型, MYC, Bcl-2

Abstract: Background and purpose: MYD88 gene has a certain mutation rate in diffuse large B-cell lymphoma (DLBCL), whereas its clinicopathological relevance is largely unknown. This study aimed to investigate the MYD88 gene mutation in DLBCL and its clinicopathological relevance. Methods: A total of 121 cases of DLBCL were collected. The immunophenotype was detected using immunohistochemistry. MYD88 gene mutation status was analyzed using a PCR assay and direct sequencing. Correlation analysis was performed using statistical methods. Results: Thirty-eight out of 121 DLBCL patients carried MYD88 L265P mutation, among whom 50 were males and 71 were females. There was no correlation between MYD88 mutation and gender. MYD88 mutation frequency in ≥60 years age group (25/62, 40.3%) was significantly higher than that in <60 years group (13/59, 22.0%) (P=0.030). This gene mutation occurred predominantly in extranodal sites, most commonly in breast (12/13, 92.3%), male reproductive system (10/11, 90.9%), female reproductive system (5/6, 83.3%) and central nervous system (4/6, 66.7%). The mutation frequency was much higher in extranodal DLBCL patients (35/98, 35.7%) than in nodal ones (2/20, 10.0%) (P=0.024). In non-GCB group, MYD88 mutation was found in 39.7% (25/63) cases, which was significantly higher than that in GCB group (10/55, 18.2%) (P=0.010). Among extranodal cases, MYD88 mutation was more significantly associated with the immunophenotype of DLBCL (P=0.003), while there was no correlation between these two parameters in nodal group (P=0.776). MYD88 mutation was more frequently seen in Bcl-2 positive group (30/77, 39.0%) than in Bcl-2 negative group (5/40, 12.5%) (P=0.003). In MYC/Bcl-2 double expression group, MYD88 mutation was significantly more common than in others (16/70, 22.9%) (P=0.034). DLBCL patients with high Ki-67 proliferation index (33/85, 38.8%) also had remarkably higher frequency of MYD88 mutation than those with low Ki-67 proliferation index (2/32, 6.3%) (P<0.001). Nevertheless neither MYC protein nor CD5 had correlation with MYD88 mutation (P=0.581 and 0.759). Conclusion: MYD88 L265P mutation in DLBCL is related with older age (≥60 years), non-GCB origin and special anatomic sites, including breast, reproductive system and central nervous system, which might also demonstrate a high proliferation index and MYC/Bcl-2 double expression rate. The survival relevance of MYD88 mutation needs to be further illustrated with larger cohort studies, and this gene mutation might provide new insights into the pathogenesis and targeted therapy for DLBCL.

Key words: Diffuse large B-cell lymphoma, MYD88 gene mutation, Immunophenotype, MYC, Bcl-2