EBV感染与霍奇金淋巴瘤肿瘤坏死因子α诱导蛋白3基因及A20蛋白表达的相关性分析
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摘要
目的:分析EB病毒(EBV)感染与霍奇金淋巴瘤肿瘤坏死因子α诱导蛋白3基因及其编码A20蛋白表达的相关性。方法:对本院收治的65例霍奇金淋巴瘤患者的临床资料与病理标本进行了回顾性分析。在肿瘤细胞丰富区制作组织芯片。通过免疫组织化学染色法对EBV编码的潜伏膜蛋白1进行测定,并用原位杂交法对EBV编码的RNA进行测定以分析其感染状态。通过荧光原位杂交技术对肿瘤坏死因子α诱导蛋白3基因表达进行测定,并用免疫组织化学染色法对EBV编码的A20蛋白表达进行测定。将所获数据纳入SPSS23. 0版统计学软件进行数据处理。结果:潜伏膜蛋白1阳性率为26. 15%(17/65),EBV编码的RNA阳性率也为26. 15%(17/65),二者符合率为100%。65例患者中A20蛋白表达丢失18例(27. 69%),存在肿瘤坏死因子α诱导蛋白3基因纯合或杂合缺失14例(21. 54%)。仅1例出现A20丢失合并肿瘤坏死因子α诱导蛋白3基因纯合缺失。相关性分析结果发现,EBV感染阴性与A20蛋白表达丢失、肿瘤坏死因子α诱导蛋白3基因缺失并无显著关系(P> 0. 05)。结论:EBV阴性与阳性的霍奇金淋巴瘤患者中,均出现A20蛋白表达丢失、肿瘤坏死因子α诱导蛋白3基因缺失,而免疫组织化学染色法与荧光原位杂交技术的检测结果并非完全一致,究其原因可能与技术因素密切相关。
Objective: To analyze the correlation of EBV infection w ith expression of TNF-α-inducing protein 3 gene and A20 protein in Hodgkin lmphoma. Methods: The clinical data and pathological specimens of 65 cases of Hodgkin's lymphoma in our hospital w ere analyzed retrospectively,and the tissue chips w ere made for the rich area of the tumor cells. The latent membrane protein 1 encoded by EBV w as measured by immunohistochemical staining,and the RNA encoded by EBV w as measured by in situ hybridization to analyze the infection state. The gene expression of tumor necrosis factorα-induced protein 3 w as detected by fluorescence in situ hybridization,and the expression of A20 protein encoded by EBV w as detected by immunohistochemical staining. The obtained data w ere processed by SPSS 23. 0 version statistical softw are. Results: The positive rate of latent membrane protein 1 w as 26. 15%( 17/65),the positive rate of EBV encoded RNA w as 26. 15%( 17/65),and the coincidence rate w as 100. 00%. In 65 patients,A20 protein expression w as lost in 18 cases( 27. 69%),and 14 cases( 21. 54%) show ed homozygous or heterozygous deletion of tumor necrosis factor-α protein 3 gene. Only 1 case show ed A20 loss combined w ith homozygous deletion of TNF-α inducible protein 3. Correlation analysis show ed that EBV infection did not significantly relate w ith expression loss of A20 protein and the gene deletion of TNF-α inducing protein 3( P > 0. 05). Conclusion: The expression loss of A20 protein and gene detection of TNF-α inducing protein 3 are found in both EBV negative and positive patients w ith Hodgkin's lymphoma,how ever the results of immunohistochemical staining and fluorescence in situ hybridization are not complete consistant,the reason may closely relate w ith the technical factors.
Objective: To analyze the correlation of EBV infection w ith expression of TNF-α-inducing protein 3 gene and A20 protein in Hodgkin lmphoma. Methods: The clinical data and pathological specimens of 65 cases of Hodgkin's lymphoma in our hospital w ere analyzed retrospectively,and the tissue chips w ere made for the rich area of the tumor cells. The latent membrane protein 1 encoded by EBV w as measured by immunohistochemical staining,and the RNA encoded by EBV w as measured by in situ hybridization to analyze the infection state. The gene expression of tumor necrosis factorα-induced protein 3 w as detected by fluorescence in situ hybridization,and the expression of A20 protein encoded by EBV w as detected by immunohistochemical staining. The obtained data w ere processed by SPSS 23. 0 version statistical softw are. Results: The positive rate of latent membrane protein 1 w as 26. 15%( 17/65),the positive rate of EBV encoded RNA w as 26. 15%( 17/65),and the coincidence rate w as 100. 00%. In 65 patients,A20 protein expression w as lost in 18 cases( 27. 69%),and 14 cases( 21. 54%) show ed homozygous or heterozygous deletion of tumor necrosis factor-α protein 3 gene. Only 1 case show ed A20 loss combined w ith homozygous deletion of TNF-α inducible protein 3. Correlation analysis show ed that EBV infection did not significantly relate w ith expression loss of A20 protein and the gene deletion of TNF-α inducing protein 3( P > 0. 05). Conclusion: The expression loss of A20 protein and gene detection of TNF-α inducing protein 3 are found in both EBV negative and positive patients w ith Hodgkin's lymphoma,how ever the results of immunohistochemical staining and fluorescence in situ hybridization are not complete consistant,the reason may closely relate w ith the technical factors.
引文
1 Taylor GS,Long HM,Brooks JM,et al.The immunology of EpsteinBarr virus-induced disease.Annu Rev Immunol,2015;33(33):787-821.
2 Vockerodt M,Yap LF,Shannon‐Lowe C,et al.The EpsteinBarr virus and the pathogenesis of lymphoma.J Pathol,2015;235(2):312-322.
3王思力,方志鸿,黄耘,等.肿瘤坏死因子α在不同类型淋巴瘤患者中的表达及其临床预后意义.中华血液学杂志,2014;35(12):1107-1110.
4 Ansell SM,Lesokhin AM,Borrello I,et al.PD-1 blockade with nivolumab in relapsed or refractory Hodgkin's lymphoma.N Engl J Med,2015;372(4):311-319.
5 Bollard CM,Gottschalk S,Torrano V,et al.Sustained complete responses in patients with lymphoma receiving autologous cytotoxic Tlymphocytes targeting Epstein-Barr virus latent membrane proteins.JClin Oncol,2014;32(8):798-808.
6尹俊杰,梁波,鲁一,等.霍奇金淋巴瘤初次治疗患者EBV感染的预后研究.中国实验血液学杂志,2016;24(5):1410-1415.
7时云飞,高子芬,刘翠苓,等.COX-2、p16INK4A、p53蛋白在经典型霍奇金淋巴瘤患者中的表达及其预后相关分析.中华血液学杂志,2015;36(11):926-932.
8吴江,宋玉,陈飞,等.TRAF1以及CD30-TRAF1信号通路在B细胞性霍奇金淋巴瘤细胞中的作用分析.临床和实验医学杂志,2016;15(2):124-126.
9 Roemer MGM,Advani RH,Ligon AH,et al.PD-L1 and PD-L2 genetic alterations define classical Hodgkin lymphoma and predict outcome.J Clin Oncol,2016;34(23):2690-2697.
10时云飞,李向红.北方地区235例霍奇金淋巴瘤临床病理特征及其EB病毒感染的相关性分析.中华病理学杂志,2015;44(2):84-89.
11 Young LS,Yap LF,Murray PG.Epstein-Barr virus:more than 50years old and still providing surprises.Nat Rev Cancer,2016;16(12):789-802.
12骞千,纪洪媛,张甜甜,等.136例中国北方汉族人群经典型霍奇金淋巴瘤与EB病毒感染的相关性研究.中国肿瘤临床,2014;(10):629-633.
13李艳芬,朱海燕.经典霍奇金淋巴瘤治疗进展.中国实验血液学杂志,2016;24(4):1237-1240.
14 Bienemann K,Borkhardt A,Klapper W,et al.High incidence of Epstein-Barr virus(EBV)‐positive Hodgkin lymphoma and Hodgkin lymphoma‐like B‐cell lymphoproliferations with EBVlatency profile 2 in children with interleukin‐2‐inducible T‐cell kinase deficiency.Histopathology,2015;67(5):607-616.
15 Xiao W,Chen WW,Sorbara L,et al.Hodgkin lymphoma variant of Richter transformation:morphology,Epstein-Barr virus status,clonality,and survival analysis-with cmparison to Hodgkin-like lesion.Hum Pathol,2016;55(9):108-116.
2 Vockerodt M,Yap LF,Shannon‐Lowe C,et al.The EpsteinBarr virus and the pathogenesis of lymphoma.J Pathol,2015;235(2):312-322.
3王思力,方志鸿,黄耘,等.肿瘤坏死因子α在不同类型淋巴瘤患者中的表达及其临床预后意义.中华血液学杂志,2014;35(12):1107-1110.
4 Ansell SM,Lesokhin AM,Borrello I,et al.PD-1 blockade with nivolumab in relapsed or refractory Hodgkin's lymphoma.N Engl J Med,2015;372(4):311-319.
5 Bollard CM,Gottschalk S,Torrano V,et al.Sustained complete responses in patients with lymphoma receiving autologous cytotoxic Tlymphocytes targeting Epstein-Barr virus latent membrane proteins.JClin Oncol,2014;32(8):798-808.
6尹俊杰,梁波,鲁一,等.霍奇金淋巴瘤初次治疗患者EBV感染的预后研究.中国实验血液学杂志,2016;24(5):1410-1415.
7时云飞,高子芬,刘翠苓,等.COX-2、p16INK4A、p53蛋白在经典型霍奇金淋巴瘤患者中的表达及其预后相关分析.中华血液学杂志,2015;36(11):926-932.
8吴江,宋玉,陈飞,等.TRAF1以及CD30-TRAF1信号通路在B细胞性霍奇金淋巴瘤细胞中的作用分析.临床和实验医学杂志,2016;15(2):124-126.
9 Roemer MGM,Advani RH,Ligon AH,et al.PD-L1 and PD-L2 genetic alterations define classical Hodgkin lymphoma and predict outcome.J Clin Oncol,2016;34(23):2690-2697.
10时云飞,李向红.北方地区235例霍奇金淋巴瘤临床病理特征及其EB病毒感染的相关性分析.中华病理学杂志,2015;44(2):84-89.
11 Young LS,Yap LF,Murray PG.Epstein-Barr virus:more than 50years old and still providing surprises.Nat Rev Cancer,2016;16(12):789-802.
12骞千,纪洪媛,张甜甜,等.136例中国北方汉族人群经典型霍奇金淋巴瘤与EB病毒感染的相关性研究.中国肿瘤临床,2014;(10):629-633.
13李艳芬,朱海燕.经典霍奇金淋巴瘤治疗进展.中国实验血液学杂志,2016;24(4):1237-1240.
14 Bienemann K,Borkhardt A,Klapper W,et al.High incidence of Epstein-Barr virus(EBV)‐positive Hodgkin lymphoma and Hodgkin lymphoma‐like B‐cell lymphoproliferations with EBVlatency profile 2 in children with interleukin‐2‐inducible T‐cell kinase deficiency.Histopathology,2015;67(5):607-616.
15 Xiao W,Chen WW,Sorbara L,et al.Hodgkin lymphoma variant of Richter transformation:morphology,Epstein-Barr virus status,clonality,and survival analysis-with cmparison to Hodgkin-like lesion.Hum Pathol,2016;55(9):108-116.