DLBCL的临床病理特征及影响预后的相关因素分析
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摘要
目的:分析弥漫大B细胞淋巴瘤(DLBCL)的临床病理特征及影响预后的相关因素。方法:对福建省肿瘤医院均获随访的94例DLBCL患者,采用免疫组化法检测BCL-2、BCL-6、MYC、CD10及MUM-1蛋白的表达,用间期荧光原位杂交法分析MYC和BCL-2基因的异常;探究DLBCL患者的临床病理特征及影响预后的相关因素。结果:94例患者中,BCL-2、BCL-6、MYC、CD10及MUM-1蛋白阳性率分别为75.53%(71/94)、58.51%(55/94)、52.13%(49/94)、15.96%(15/94)、34.04%(32/94)。MYC基因异常检出率为20.93%(9/43),BCL-2基因异常检出率为44.00%(22/50),2种基因异常均为多拷贝;MYC与BCL-2基因同时异常者2例(2.13%)。94例患者3年中位生存时间为21.79(2-36)个月,1、3年总生存率分别为82.98%和64.89%。单因素分析结果发现,ECOG评分≥2、国际预后指数(IPI)分级增加、BCL-6蛋白阳性表达、MYC和及BCL-2基因同时异常均是影响预后的危险因素(P<0.05)。COX风险模型回归分析结果发现,IPI分级、ECOG评分及治疗方法均是影响患者预后效果的独立因素(P<0.05)。结论:IPI分级、ECOG评分及治疗方法对DLBCL患者预后效果的影响较大,化疗联合放疗或手术的治疗方法可以明显提高患者的预后效果。
Objective: To analyze the clinicopathological features and prognostic factors of patients with diffuse large B-cell lymphoma( DLBCL).Methods: Ninety-four cases of DLBCL follow ed up were selected in Fujian Tumor Hospital.The immunohistochemistry method was used to detect the protein expressions of BCL-2 BCL-6,MYC,CD10 and MUM-1,the gene abnormalities of MYC and BCL-2 were analyzed by fluorescence in situ hybridization,and the clinical pathological features and the related factors affecting prognosis in the patients with DLBCL were analyzed.Results:The protein positive rates of BCL-2,BCL-6,MYC,CD10 and MUM-1 in 94 patients were 75.53%(71/94),58.51%(55/94),52.13%( 49/94),15.96%( 15/94) and 34.04%( 32/94) respectively.The detection rate of MYC gene abnormality was 20.93%(9/43) and the detection rate of BCL-2 gene abnormality was 44%( 22/50); 2 kinds of gene abnormalities were of multiple copies,and 2 cases( 2.13%) were abnormal in MYC and BCL-2 genes simultaneously.The median survival time of 3 years in 94 patients was 21.79 months(2-36 months),and the overall survival rates of 1 and 3 years were 82.98% and 64.89% respectively.Single factor analysis revealed that the high ECOGscore( ≥ 2),high international prognostic index( IPI) classification,positive expression of BCL-6 protein,and MYC and BCL-2 gene simultaneously abnormal were the risk factors influencing the prognosis( all P < 0.05).COX regression analysis showed that IPI classification, ECOGscore and treatment methods were independent factors influencing the prognosis( all P < 0.05).Conclusion: IPI classification,ECOGscore and treatment methods have greater impacts on the prognosis of patients with DLBCL.Chemotherapy combined with radiotherapy or surgical treatment can significantly improve the prognosis of patients.
Objective: To analyze the clinicopathological features and prognostic factors of patients with diffuse large B-cell lymphoma( DLBCL).Methods: Ninety-four cases of DLBCL follow ed up were selected in Fujian Tumor Hospital.The immunohistochemistry method was used to detect the protein expressions of BCL-2 BCL-6,MYC,CD10 and MUM-1,the gene abnormalities of MYC and BCL-2 were analyzed by fluorescence in situ hybridization,and the clinical pathological features and the related factors affecting prognosis in the patients with DLBCL were analyzed.Results:The protein positive rates of BCL-2,BCL-6,MYC,CD10 and MUM-1 in 94 patients were 75.53%(71/94),58.51%(55/94),52.13%( 49/94),15.96%( 15/94) and 34.04%( 32/94) respectively.The detection rate of MYC gene abnormality was 20.93%(9/43) and the detection rate of BCL-2 gene abnormality was 44%( 22/50); 2 kinds of gene abnormalities were of multiple copies,and 2 cases( 2.13%) were abnormal in MYC and BCL-2 genes simultaneously.The median survival time of 3 years in 94 patients was 21.79 months(2-36 months),and the overall survival rates of 1 and 3 years were 82.98% and 64.89% respectively.Single factor analysis revealed that the high ECOGscore( ≥ 2),high international prognostic index( IPI) classification,positive expression of BCL-6 protein,and MYC and BCL-2 gene simultaneously abnormal were the risk factors influencing the prognosis( all P < 0.05).COX regression analysis showed that IPI classification, ECOGscore and treatment methods were independent factors influencing the prognosis( all P < 0.05).Conclusion: IPI classification,ECOGscore and treatment methods have greater impacts on the prognosis of patients with DLBCL.Chemotherapy combined with radiotherapy or surgical treatment can significantly improve the prognosis of patients.
引文
1 Visco C,Tzankov A,Xu-Monette ZY,et al.Patients with diffuse large B-cell lymphoma of germinal center origin with BCL2 translocations have poor outcome,irrespective of MYC status:a report from an International DLBCL rituximab-CHOP Consortium Program Study.Haematologica,2013;98(2):255-263.
2 Chapuy B,Mc Keown MR,Lin CY,et al.Discovery and characterization of super-enhancer-associated dependencies in diffuse large Bcell lymphoma.Cancer cell,2013;24(6):777-790.
3 中华医学会血液学分会,中国抗癌协会淋巴瘤专业委员会.中国弥漫大B细胞淋巴瘤诊断与治疗指南(2013年版).中华血液学杂志,2013;34(9):816-819.
4 Dekker JD,Park D,Shaffer AL,et al.Subtype-specific addiction of the activated B-cell subset of diffuse large B-cell lymphoma to FOXP1.Proc Natl Acad Sci,2016;113(5):E577-E586.
5 Xu-Monette ZY,Dabaja BS,Wang X,et al.Clinical features,tumor biology,andprognosisassociated with MYC rearrangement and Myc overexpression in diffuse large B-cell lymphoma patients treated with rituximab-CHOP.Mod Pathol,2015;28(12):1555-1573.
6 张宇,杨明珍.HBV相关弥漫大B细胞淋巴瘤临床特征、BCL-2 、CMYC表达及预后分析.安徽医科大学学报,2017;52(4):570-574.
7 柴成国,张建军,李宁,等.P53、C-MYC和BCL-6基因异常在弥漫性大B细胞淋巴瘤中的临床意义.中国实验血液学杂志,2016;24(1):89-93.
8 雷秦,王娟.Bcl-2与Bcl-6在弥漫性大B细胞淋巴瘤中的表达及意义.现代检验医学杂志,2015;30(5):94-96.
9 Zappasodi R,Ruggiero G,Guarnotta C,et al.HSPH1 inhibition downregulates Bcl-6 and c-Mycand hampers the growth of human aggressive B-cell non-Hodgkin lymphoma.Blood,2015;125(11):1768-1771.
10 黄文亭,吕宁,郭蕾,等.c-myc基因在弥漫性大B细胞淋巴瘤中的意义及其应用.中华病理学杂志,2013;42(9):638-640.
11 杨莉洁,周伟.弥漫大B细胞淋巴瘤组织中Bcl-2、NF-κB、c-Myc蛋白表达及临床意义.中国医学前沿杂志(电子版),2016;8(11):125-128.
12 Zhou K,Xu D,Cao Y,et al.C-MYC aberrations as prognostic factors in diffuse large B-cell lymphoma:a meta-analysis of epidemiological studies.PLo S One,2014;9(4):e95020.
13 魏华萍,赵小利,王全顺,等.BCL-2蛋白在弥漫大B细胞淋巴瘤中的表达及预后价值.中国实验血液学杂志,2015;23(6):1607-1611.
14 孟亚红,孙丽华.弥漫性大B细胞淋巴瘤中Bcl-6、Bcl-2和NF-κB的表达及临床意义.中国实验诊断学,2017;21(3):510-512.
15 Ying CY,Dominguez-Sola D,Fabi M,et al.MEF2B mutations lead to deregulated expression of the oncogene BCL-6 in diffuse large B cell lymphoma.Nat Immunol,2013;14(10):1084-1092.
2 Chapuy B,Mc Keown MR,Lin CY,et al.Discovery and characterization of super-enhancer-associated dependencies in diffuse large Bcell lymphoma.Cancer cell,2013;24(6):777-790.
3 中华医学会血液学分会,中国抗癌协会淋巴瘤专业委员会.中国弥漫大B细胞淋巴瘤诊断与治疗指南(2013年版).中华血液学杂志,2013;34(9):816-819.
4 Dekker JD,Park D,Shaffer AL,et al.Subtype-specific addiction of the activated B-cell subset of diffuse large B-cell lymphoma to FOXP1.Proc Natl Acad Sci,2016;113(5):E577-E586.
5 Xu-Monette ZY,Dabaja BS,Wang X,et al.Clinical features,tumor biology,andprognosisassociated with MYC rearrangement and Myc overexpression in diffuse large B-cell lymphoma patients treated with rituximab-CHOP.Mod Pathol,2015;28(12):1555-1573.
6 张宇,杨明珍.HBV相关弥漫大B细胞淋巴瘤临床特征、BCL-2 、CMYC表达及预后分析.安徽医科大学学报,2017;52(4):570-574.
7 柴成国,张建军,李宁,等.P53、C-MYC和BCL-6基因异常在弥漫性大B细胞淋巴瘤中的临床意义.中国实验血液学杂志,2016;24(1):89-93.
8 雷秦,王娟.Bcl-2与Bcl-6在弥漫性大B细胞淋巴瘤中的表达及意义.现代检验医学杂志,2015;30(5):94-96.
9 Zappasodi R,Ruggiero G,Guarnotta C,et al.HSPH1 inhibition downregulates Bcl-6 and c-Mycand hampers the growth of human aggressive B-cell non-Hodgkin lymphoma.Blood,2015;125(11):1768-1771.
10 黄文亭,吕宁,郭蕾,等.c-myc基因在弥漫性大B细胞淋巴瘤中的意义及其应用.中华病理学杂志,2013;42(9):638-640.
11 杨莉洁,周伟.弥漫大B细胞淋巴瘤组织中Bcl-2、NF-κB、c-Myc蛋白表达及临床意义.中国医学前沿杂志(电子版),2016;8(11):125-128.
12 Zhou K,Xu D,Cao Y,et al.C-MYC aberrations as prognostic factors in diffuse large B-cell lymphoma:a meta-analysis of epidemiological studies.PLo S One,2014;9(4):e95020.
13 魏华萍,赵小利,王全顺,等.BCL-2蛋白在弥漫大B细胞淋巴瘤中的表达及预后价值.中国实验血液学杂志,2015;23(6):1607-1611.
14 孟亚红,孙丽华.弥漫性大B细胞淋巴瘤中Bcl-6、Bcl-2和NF-κB的表达及临床意义.中国实验诊断学,2017;21(3):510-512.
15 Ying CY,Dominguez-Sola D,Fabi M,et al.MEF2B mutations lead to deregulated expression of the oncogene BCL-6 in diffuse large B cell lymphoma.Nat Immunol,2013;14(10):1084-1092.