弥漫大B细胞淋巴瘤患者临床病理特征及预后分析

Clinicopathological characteristics and prognosis of patients with diffuse large B-cell lymphoma

目的 探讨弥漫大B细胞淋巴瘤(DLBCL)患者的临床病理特征、分子遗传学特征及预后。 方法 回顾性分析北京大学第三医院及北京大学基础医学院2008年1月至2015年12月会诊及常规外检的152例DLBCL患者的临床病理资料,采用免疫组织化学法检测CD10、bcl-6、MUM1、GCET1、FOXP1的表达情况,采用原位杂交检测EB病毒编码小RNA;采用荧光原位杂交(FISH)检测bcl-2、bcl-6和c-myc基因异常情况,筛选双重打击淋巴瘤(DHL)。采用Kaplan-Meier法进行生存分析。 结果 152例DLBCL中,男女比例为1.49∶1,中位发病年龄59岁(7~90岁),原发于淋巴结内79例(52.0%)。全部患者中位总生存(OS)时间为16个月(1~101个月),1、3、5年OS率分别为70.2%、44.7%及30.3%。R-CHOP方案治疗组OS好于CHOP方案治疗组及未治疗组( P =0.001)。137例进行双重打击免疫组织化学评分(DHS评分)的患者中,0分56例,1分57例,2分24例,不同DHS评分组间OS差异无统计学意义( P =0.311)。FISH检测结果,29例检测c-myc基因患者中,c-myc基因断裂2例,扩增3例;26例行bcl-2基因检测的患者中,bcl-2扩增2例;26例行bcl-6基因检测的患者中,bcl-6扩增2例,基因断裂3例。1例患者同时存在myc和bcl-2基因扩增,合并bcl-6基因断裂,即三重打击淋巴瘤。DHS评分0分组发现1例双基因异常,1分组发现1例单基因异常,2分组发现5例单基因异常及1例三基因异常,基因异常与蛋白表达不一致。 结论 我国DLBCL中DHL发生率低,基因异常以c-myc或bcl-2、bcl-6单基因异常为主。

Objective To investigate the clinicopathological and molecular genetic characteristics and prognosis of patients with diffuse large B-cell lymphoma(DLBCL).Methods The clinicopathological data of 152 DLBCL patients receiving consultation and routine physical examination in Peking University Third Hospital and Peking University School of Basic Medicine from January 2008 to December 2015 were retrospectively analyzed.Immunohistochemistry was used to detect the expressions of CD10,bcl-6,MUM1,GCET1,FOXP1.EB virus encoded small RNA(EBV-EBER)was detected by using in situ hybridization.The aberrations of bcl-2,bcl-6 and c-myc genes were detected by using fluorescence in situ hybridization(FISH)to screen double-hit lymphoma(DHL).Kaplan-Meier method was used to make survival analysis.Results Among 152 cases of DLBCL,the ratio of male to female was 1.49:1,the median age of onset was 59 years(7-90 years),and 79 cases(52.0%)were primary lymph nodes.The median overall survival(OS)time of all cases was 16 months(1-101 months).The 1-year,3-year and 5-year OS rates were 70.2%,44.7%,30.3%,respectively.The OS of R-CHOP treatment group was better than that of CHOP treatment group and untreated group(P=0.001).Among all 137 patients receiving double-hit histochemistry score(DHS),there were 56 cases with 0 score,57 cases with 1 score,24 cases with 2 scores;and the difference in the OS of different DHS score groups(P=0.311).FISH detection showed that among 29 cases achieving results of c-myc gene detection,there were 2 cases of splitting gene and 3 cases of gene amplification;among 26 cases achieving results of bcl-2 gene detection,2 cases had bcl-2 gene amplification;among 26 cases achieving results of bcl-6 gene detection,2 cases had bcl-6 gene amplification and 3 cases had splitting gene.It was found that myc and bcl-2 genes were amplified simultaneously in 1 case,accompanied with bcl-6 gene splitting,which was called triple-hit lymphoma.In DHS 0-score group,1 case of double gene abnormality was found,and 1 case of single gene abnormality was found in group 1-score;in group 2-score,5 cases were single gene abnormality and 1 case was three gene abnormality,so the gene abnormality was inconsistent with the protein expression.Conclusions The incidence of DHL in DLBCL patients in China is low.The major gene abnormalities are c-myc or bcl-2,bcl-6 single gene abnormalities.