摘要
目的:检查弥漫大B细胞淋巴瘤(diffuse large B-cell lymphoma,DLBCL)中肿瘤坏死因子诱导蛋白3基因(tumor necrosis factor,alpha-induced protein 3 gene,A20基因)突变情况,探讨其对DLBCL进展、预后及肿瘤耐药的影响。方法:收集104例DLBCL病例及其临床资料并随访部分病例,应用免疫组织化学染色检测肿瘤细胞中P-g P和Ki-67蛋白表达;聚合酶链反应扩增和DNA测序检测A20基因外显子3、6、7突变情况;分析A20基因与DLBCL临床病理特征及预后的关系。结果:104例DLBCL中,A20基因3号外显子存在错义突变,总突变率17.3%。其中第73位突变率在ABC-DLBCL与GCB-DLBCL病例之间差异具有统计学意义(18.5%vs.2.5%,P=0.010);在临床分期晚和高IPI指数的DLBCL病例中,A20突变率明显高于相应的早临床分期和低IPI指数病例(P<0.05)。在A20基因突变与未突变病例之间P-g P表达的差异有统计学意义(16/18 vs.52/86,P=0.021),Ki-67低表达与高表达病例之间差异有统计学意义(低表达/高表达:1/17 vs.26/60,P=0.030);与未突变病例比较,A20基因突变的DLBCL病例复发率有增高的趋势(P=0.06),生存状况较差(P=0.016)。结论:DLBCL病例中A20基因的突变对DLBCL的临床病理特征及生存状况有一定影响,A20基因突变可能是DLBCL预后不良的相关因子。
Objective：To detect A20 mutation and to investigate its relationship with clinicopathologic features, prognosis, and re-sistance to therapy of diffuse large B cell lymphoma （DLBCL）. Methods：A total of 104 cases with DLBCL and their clinical data were collected;follow-up was performed on a few of DLBCL patients. The expression of P-gP and Ki-67 protein was detected with immuno-histochemical staining. The A20 gene mutation in exons 3, 6, and 7 were examined by polymerase chain reaction and DNA sequencing. Finally, the correlation of genetic abnormality of A20 with clinicopathologic features was analyzed. Results：Missense mutation in ex-on 3 of A20 gene was identified in 18 of 104 patients （17.3%）. The A20 gene mutation at site 73 of exon 3 was greater in the cases with activated B cell-like-DLBCL than with germinal center B-cell-like-DLBCL （18.5%vs. 2.5%, P=0.010）. In contrast to the advanced clin-ical stage and high International Prognostic Index （IPI） cases, the rate of A20 mutation was superior to the opposite （P〈0.05）. The ex-pression for P-gP was higher in the cases with mutation than that of those with wild-type A20 gene （16/18 vs. 52/86, P=0.021）. The dif-ference in A20 mutation between the groups of low and high positive expression for Ki-67 （1/17 vs. 26/60, P=0.030） was significant. DLBCL with A20 mutation had an increasing recurrence tendency （P=0.06） and a worse survival （P=0.016） compared with those with wild-type A20 gene. Conclusion：The A20 mutation has a certain influence on the clinicopathologic characteristics and survival condi-tions of BLBCL patients. Probably, A20 mutation is a factor associated with a poor prognosis of DLBCL.
出处
《中国肿瘤临床》
CAS
CSCD
北大核心
2015年第20期1018-1024,共7页
Chinese Journal of Clinical Oncology
基金
supported by the National Natural Science Foundation of China(No.81160299)
