MYC、BCL-2和BCL-6检测在弥漫性大B细胞淋巴瘤患者预后判断中的价值
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摘要
目的:分析BCL-2、BCL-6和MYC检测在弥漫性大B细胞淋巴瘤(DLBCL)患者中预后判断中的价值。方法:收集2012年3月至2015年3月本院收治的DLBCL患者163例患者的淋巴瘤组织标本,采用免疫组织化学方法检测患者BCL-2、BCL-6和MYC的表达水平,并用间期荧光原位杂交技术对IGH/BCL-2融合、BCL-6基因断裂及MYC基因断裂进行检测,进一步分析BCL-2、BCL-6和MYC表达水平与DLBCL患者临床病理特征及预后的相关性。结果:MYC、BCL-2及BCL-6均呈现棕黄色或棕褐色的阳性信号,其中MYC主要于细胞膜上呈现阳性表达,BCL-2主要于细胞质及局部细胞膜上呈现阳性表达,BCL-6主要于细胞核上呈现阳性表达。ECOG体能状态评分≥2分者BCL-2表达水平较<2分者明显升高,且免疫亚型为CD5~+、生发中心B细胞样(GCB)者BCL-2表达水平较非GCB者明显升高(P<0.05);国际预后指数(IPI)评分为3-5者MYC表达水平较0-2分者明显升高(P<0.05);免疫亚型为CD5~+、GCB者BCL-6表达水平较非GCB者明显降低(P<0.05)。经Cox多变量分析结果发现,BCL-2、BCL-6和MYC的表达水平与DLBCL患者总生存期和无进展生存期均存在显著关系(P<0.05)。结论:BCL-2、BCL-6和MYC作为重要的分子标志物,在评估DLBCL患者预后中具有较高的判断价值。
Objective: To analyze the prognostic value of BCL-2, BCL-6 and MYC in patients with diffuse large B cell lymphoma(DLBCL). Methods: One hundred and sixty three cases of DLBCL in our hospital from March 2012 to March 2015 were selected. The specimens of lymphoma tissue of patients were collected. The expression of BCL-2, BCL-6 and MYC was detected by immunohistochemical method. The fusion of IGH/BCL-2, the gene breakage of BCL-6 and MYC were detected by interphase fluorescence in situ hybridization. The correlation of the expression levels of BCL-2,BCL-6 and MYC with the clinicopathological features and prognosis in the patients with DLBCL was further analyzed.Results: MYC, BCL-2 and BCL-6 showed pale brown or reddish brown positive signals, among them MYC mainly positively expressed on the cell membrane, and BCL-2 mainly expressed on the cytoplasm and local cell membrane, and BCL-6 mainly expressed in the nucleus. The expression level of BCL-2 in ECOG physical status score 2 was higher than that in patients with <2 scores, and the expression level of BCL-2 in CD5~+ and germinal center B-cell-like(GCB) was significantly higher than that in patients with non-GCB(P<0.05), and the international prognostic index(IPI) for 3-5 scores at the MYC expression level was significantly higher than that of the 0-2 score(P<0.05); the expression level of BCL-6 in immune subtype CD5~+ and GCB was significantly lower than that in non-GCB (P< 0.05). The results of Cox multivariate analysis showed that the expression level of BCL-2, BCL-6 and MYC significant correlate with the overall survival and progression-free survival (P< 0.05) of the patients with DLBCL. Conclusion: BCL-2, BCL-6 and MYC as important molecular markers are of high value for evaluating the prognosis of patients with DLBCL.
Objective: To analyze the prognostic value of BCL-2, BCL-6 and MYC in patients with diffuse large B cell lymphoma(DLBCL). Methods: One hundred and sixty three cases of DLBCL in our hospital from March 2012 to March 2015 were selected. The specimens of lymphoma tissue of patients were collected. The expression of BCL-2, BCL-6 and MYC was detected by immunohistochemical method. The fusion of IGH/BCL-2, the gene breakage of BCL-6 and MYC were detected by interphase fluorescence in situ hybridization. The correlation of the expression levels of BCL-2,BCL-6 and MYC with the clinicopathological features and prognosis in the patients with DLBCL was further analyzed.Results: MYC, BCL-2 and BCL-6 showed pale brown or reddish brown positive signals, among them MYC mainly positively expressed on the cell membrane, and BCL-2 mainly expressed on the cytoplasm and local cell membrane, and BCL-6 mainly expressed in the nucleus. The expression level of BCL-2 in ECOG physical status score 2 was higher than that in patients with <2 scores, and the expression level of BCL-2 in CD5~+ and germinal center B-cell-like(GCB) was significantly higher than that in patients with non-GCB(P<0.05), and the international prognostic index(IPI) for 3-5 scores at the MYC expression level was significantly higher than that of the 0-2 score(P<0.05); the expression level of BCL-6 in immune subtype CD5~+ and GCB was significantly lower than that in non-GCB (P< 0.05). The results of Cox multivariate analysis showed that the expression level of BCL-2, BCL-6 and MYC significant correlate with the overall survival and progression-free survival (P< 0.05) of the patients with DLBCL. Conclusion: BCL-2, BCL-6 and MYC as important molecular markers are of high value for evaluating the prognosis of patients with DLBCL.
引文
1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.
2 Zappasodi R, Ruggiero G, Guarnotta C, et al. HSPH1 inhibition downregulates BCL-6 andc-Mycand hampers the growth of human aggressive B-cell non-Hodgkin lymphoma. Blood, 2015; 125(11):1768-1771.
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 Chapuy B, McKeown MR, Lin CY, et al. Discovery and characterization of super-enhancer-associated dependencies in diffuse large B cell lymphoma. Cancer cell, 2013; 24(6):777-790.
5 Visco C, Tzankov A, Xu-Monette ZY, et al. Patients with diffuse large B-cell lymphoma ofgerminal center origin with BCL2translocations have poor outcome, irrespective of MYCstatus:a report from an International DLBCL rituximab-CHOP Consortium Program Study. Haematologica, 2013; 98(2):255-263.
6 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.
7 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.
8 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.
9 Xu-Monette ZY, Dabaja BS, Wang X, et al. Clinical features, tumor biology, and prognosisassociated with MYC rearrangement and Myc overexpression in diffuse large B-cell lymphoma patients treated with rituximab-CHOP. Mod Pathol, 2015; 28(12):1555-1573.
10 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.
11 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.
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. PLoS One, 2014; 9(4):e95020.
13 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.
14 Ying CY, Dominguez-Sola D, Fabi M, et al. MEF2B mutations lead to deregulated expression of the oncogene BCL6 in diffuse large B cell lymphoma. Nat Immunol, 2013; 14(10):1084-1092.
15 Perry AM,Alvarado-Bernal Y, Laurini JA, et al. MYC and BCL2protein expression predicts survival in patients with diffuse large B-cell lymphoma. Br J Haematol,2014;165(3):382-391.
2 Zappasodi R, Ruggiero G, Guarnotta C, et al. HSPH1 inhibition downregulates BCL-6 andc-Mycand hampers the growth of human aggressive B-cell non-Hodgkin lymphoma. Blood, 2015; 125(11):1768-1771.
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 Chapuy B, McKeown MR, Lin CY, et al. Discovery and characterization of super-enhancer-associated dependencies in diffuse large B cell lymphoma. Cancer cell, 2013; 24(6):777-790.
5 Visco C, Tzankov A, Xu-Monette ZY, et al. Patients with diffuse large B-cell lymphoma ofgerminal center origin with BCL2translocations have poor outcome, irrespective of MYCstatus:a report from an International DLBCL rituximab-CHOP Consortium Program Study. Haematologica, 2013; 98(2):255-263.
6 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.
7 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.
8 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.
9 Xu-Monette ZY, Dabaja BS, Wang X, et al. Clinical features, tumor biology, and prognosisassociated with MYC rearrangement and Myc overexpression in diffuse large B-cell lymphoma patients treated with rituximab-CHOP. Mod Pathol, 2015; 28(12):1555-1573.
10 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.
11 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.
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. PLoS One, 2014; 9(4):e95020.
13 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.
14 Ying CY, Dominguez-Sola D, Fabi M, et al. MEF2B mutations lead to deregulated expression of the oncogene BCL6 in diffuse large B cell lymphoma. Nat Immunol, 2013; 14(10):1084-1092.
15 Perry AM,Alvarado-Bernal Y, Laurini JA, et al. MYC and BCL2protein expression predicts survival in patients with diffuse large B-cell lymphoma. Br J Haematol,2014;165(3):382-391.