A20基因甲基化对弥漫性大B细胞性淋巴瘤的影响

Effects of the methylation of A20 gene on diffuse large B cell lymphoma

目的检测弥漫性大B细胞性淋巴瘤(DLBCL)中A20基因甲基化状况,探讨其对DLBCL临床过程及预后的影响。方法通过组织学观察及免疫表型检测筛选104例DLBCL,收集其临床病理资料及随访;并以甲基化特异性PCR(MSP)法检测A20基因启动子区5'Cp G岛甲基化的情况;以免疫组化SP法检测肿瘤细胞P糖蛋白(Pg P)和Ki-67蛋白的表达。结果 104例DLBCL中,A20基因甲基化率为26%(27/104),活化后B细胞样(ABC)-DLBCL组甲基化率(35.4%)高于生发中心B细胞样(GCB)DLBCL组(10.2%)(P<0.05);Pg P阳性率65.4%(68/104),A20基因甲基化组Pg P阳性率(85.2%)明显高于无甲基化组(58.4%)(P<0.05);A20基因甲基化与非甲基化组之间Ki-67高表达病例与低表达病例均无明显差异(P>0.05);A20基因甲基化病例的复发率明显高于无甲基化病例(P<0.05);生存分析发现,两组病例的生存状况差异不显著。结论 DLBCL部分病例存在A20基因甲基化,以ABC-DBLCL病例多见。A20基因甲基化与DLBCL的复发有关,且可能通过NF-κB异常活化而促进肿瘤细胞Pg P蛋白表达,从而影响DLBCL的化疗效果。

Objective To detect the methylation of A20 gene,and to investigate the relationship between the methylation of A20 gene and clinicopathological features,prognosis in the DLBCL.Methods 104 cases with DLBCL were selected by reviewing of morphology and examining immunohistochemical phenotype.The methylation of A20 gene was detected by methylation-specific PCR（ MSP）.The expression of Pg P and Ki-67 was detected by immunohistochemical stain（ IHC）.Collection of clinicopathological data,follow-up and statistical analysis were done.Results The methylation of A20 gene was identified in 27 of 104 patiens（ 26%,27 /104,）.It was more frequent in ABC-DLBCL（ 23 /65,35.4%） than GCBDLBCL（ 4 /39,10.2%,P = 0.003）;The positive expression for Pg P was 65.3%（ 68 /104）.The stastistical difference in positive expression for Pg P was found between the cases with methylation（ 23） and non-methylation（ 45） of A20 gene（ P =0.012）;Both the cases of high and low expression for Ki67 were no statistical significance between the cases with methylation and non-methylation（ P = 0.607）.Relapse was more common in the patient with methylation of A20（ 14 /18）gene than those with non-methylation（ 20 /44,P = 0.017）;There was no difference in survival between two groups.Conclusion The methylation of A20 gene exists in some patients with DLBCL,especially in those with ABC-DLBCL.It associates with the relapse of the lymphoma.It also may associate with drug-resistant of DLBCL by indirectly promoting the expression of Pg P,through a way decreasing negative regulation of NF-ΚB.