70例弥漫大B细胞淋巴瘤相关预后因素的分析
摘要
目的:研究弥漫大B细胞淋巴瘤的相关预后因素及Ki-67、bcl-6的表达与预后的关系。方法:收集甘肃省肿瘤医院、兰大一院、兰大二院2001-2008年诊断为弥漫大B细胞淋巴瘤的临床资料及病理切片与蜡块,共计70例。其中男性40例,女性30例,年龄≥60岁者24例,41-59岁者20例,≤40岁者26例,中位年龄47岁。复查全部病例的临床、病理资料(包括HE切片及免疫组化切片),并补做缺失的免疫组化染色,按照WHO新分类对所有病例重新分类。对70例病例进行随访,最长随访时间60个月,应用SPSS 13.0统计软件包进行统计学处理,以p＜0.05为显著性差异,有统计学意义,计数资料比较用χ~2检验,分别比较各个预后因素的治愈率,进行COX回归分析,Kaplan-Meier生存分析法列出相关生存曲线图,Log-Rank检验比较各个预后因素的生存率,Spearman等级相关分析了解与进展期弥漫大B细胞淋巴瘤生存率相关的预后因素。根据CD10、Bcl-6和MUM1染色,区别生发中心B细胞型(GCB)与非生发中心B细胞型(non-GCB),观察其预后。结果:年龄小、临床分期早、IPI评分低、无临床症状、淋巴结原发、GCB型预后较好。Ⅲ、Ⅳ期病例中,LDH及β_2-MG两项指标均正常的患者预后要好于任一指标偏高者,其中两项指标均偏高的患者预后最差。Ki-67高表达提示肿瘤的高侵袭性,预后差。bcl-6在弥漫大B细胞中普遍高表达,但阳性表达与预后无统计学意义。结论:弥漫大B细胞淋巴瘤的预后与年龄、分期、IPI评分、LDH、β_2-MG、有无临床症状、原发部位有关,年龄、分期、IPI、LDH为独立影响因素;在Ⅲ、Ⅳ期病例中,LDH及β_2-MG是评价预后的重要指标;Ki-67高表达与预后有关,bcl-6在DLBCL中普遍高表达,但与预后无统计学意义。
Objective: to explore the prognostic factors of diffuse large B-cell lymphoma (DLBCL) and to investigate the correlation between the expression of Ki-67 and bcl-6 and prognosis in DLBCL. Methods: Collected 70 cases of diffuse large B-cell lymphoma, incloding pathological and medical records and immunohisto chemical wax from 2001 to 2008 in Tumour Hospital of Gansu Province,the First Affiliated Hospital of Lanzhou University and the Second Affiliated Hospital of Lanzhou University. 40 are male and 30 are female , 24 examples of them are orlder than 60 years.20 of them from41 to 59 years old , 26 of them are younger than 40 years. They are hit by place age 47-year-old. Reexamine the clinical all case pathological mechanism data, the parallel corresponding immunity group spends dyeing , case classifies again according to that WHO classifies newly to possessions. Carry out a follow-up on 70 example case, the longest follow-up time 60 months. explore the prognostic factors of diffuse large B-cell lymphoma through the COX Regression , the Spearman correlation analysis,the Kaplan-Meier survival analysis and Logrank. According to CD10 , Bcl-6 and MUM1 dyeing, develop GCB and the non-GCB, observing the prognosis. The data was handlesd through 13.0 statistics software package applying SPSS , and bear out the conclusion. Results : Earlier clinical stage, low IPI score, low age, no clinical symptoms, primary nodal ,GCB had better prognosis than later stage, high IPI score, older, having clinical symptoms,primary outside nodal and non-GCB. In the records of III or IV clinical stages , the LDH andβ_2-MG were important parameters, two parameters had a better prognosis in patients with normal than only one with normal. They all with higher than normal had the worst prognosis . Pathologic data, Ki-67 high expression hint of higher invasion, worse prognosis, and BCL-6 in the diffuse large B cell in common with high expression, but further study would be done. Conclusion: prognosis of diffuse large B cell lymphoma had related with not only age, clinic stages, IPI stage, LDH,β_2-MG, B symptoms, the primary site but also Ki -67 index. And BCL-6 had high expression in DLBCL.
Objective: to explore the prognostic factors of diffuse large B-cell lymphoma (DLBCL) and to investigate the correlation between the expression of Ki-67 and bcl-6 and prognosis in DLBCL. Methods: Collected 70 cases of diffuse large B-cell lymphoma, incloding pathological and medical records and immunohisto chemical wax from 2001 to 2008 in Tumour Hospital of Gansu Province,the First Affiliated Hospital of Lanzhou University and the Second Affiliated Hospital of Lanzhou University. 40 are male and 30 are female , 24 examples of them are orlder than 60 years.20 of them from41 to 59 years old , 26 of them are younger than 40 years. They are hit by place age 47-year-old. Reexamine the clinical all case pathological mechanism data, the parallel corresponding immunity group spends dyeing , case classifies again according to that WHO classifies newly to possessions. Carry out a follow-up on 70 example case, the longest follow-up time 60 months. explore the prognostic factors of diffuse large B-cell lymphoma through the COX Regression , the Spearman correlation analysis,the Kaplan-Meier survival analysis and Logrank. According to CD10 , Bcl-6 and MUM1 dyeing, develop GCB and the non-GCB, observing the prognosis. The data was handlesd through 13.0 statistics software package applying SPSS , and bear out the conclusion. Results : Earlier clinical stage, low IPI score, low age, no clinical symptoms, primary nodal ,GCB had better prognosis than later stage, high IPI score, older, having clinical symptoms,primary outside nodal and non-GCB. In the records of III or IV clinical stages , the LDH andβ_2-MG were important parameters, two parameters had a better prognosis in patients with normal than only one with normal. They all with higher than normal had the worst prognosis . Pathologic data, Ki-67 high expression hint of higher invasion, worse prognosis, and BCL-6 in the diffuse large B cell in common with high expression, but further study would be done. Conclusion: prognosis of diffuse large B cell lymphoma had related with not only age, clinic stages, IPI stage, LDH,β_2-MG, B symptoms, the primary site but also Ki -67 index. And BCL-6 had high expression in DLBCL.
引文
[1]Harris NL,Jaffe ES,Stein H,et al.A revised European-American classification of lymphoid neoplasm:a proposal from the International Lymphoma Study Group[J].Blood,1994,84:1361-1392.
[2]Gatter KC,Wanke RA,Diffuse large B-cell lymphoma.In:Jaffe ES,Harris NL,Stein H,et al.WHO Classification of Tumors:Pathology and Genetics of Internationa[J].Agency for Research on Cancer(IARC) Press,2001.171-174.
[3]Jaffe ES,Harris NL,Stein H,et al.World Health Organization Classification of Tumours.Pathology and Genetics of Tumours of Haematopoietic and lymphoid tissues[M],IARC Press:Lyon,2001,111-235.
[4]Jafe ES,Harris NL,Stein H,et al.World Health Organization Classification of Tumors Pathology and Genetics:Tumors of Haematopoietic and Lymphoid Tissues[M].IARC Press:Lyon,2001:171-174.
[5]Amytage JO,Weisenburger DD.New approach to classifying non-Hodgkin's lymphona:clinical features of the major histologic sublypes.Non-Hodgkin's lymphona Classification profect[J].J clin Oncol,1998,16:2780-2795.
[6]Harris NL,Stein H,Coupland SE,et al.New approaches to lymphoma diagnosis[J].Hematology,2001(Am soc Hematol Educ Program),194-220.
[7]张莉,曹永清,符岭华,等.湖南省恶性淋巴瘤、白血病流行病学调查[J].中国现代医学杂志,1998,8(12):25.
[8]Holly EA,Gautam M,Bracci PM.Comparison of interviewed and non-interviewed non- Hodgkin's lymphoma(NHL)Patients in the San Francis-co Bay A rea[J].Ann Epidemiol,2002,12(6):419.
[9]Goldman,Bennett.西氏内科学[M].第21版.第5分册.世界图书出版公司,2005.223.
[10]Wilder KB,Rodriguez MA,Medeiros LJ,et al.International prognostic index-based outcomes for diffuse large B-cell lymphomas[J].Cancer,2002.94:3083-3088.
[11]Hans CP,Weisenburger D,Greiner T,Gascoyne R,Delabie J,Ott G.Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using microarray.Blood,2004,103(1):275-282.
[12]Young-Ha Oh,Chan-Kum Park.Prognostic Evaluation of Nodal Diffuse Large B cell lymphoma by Immunohistochemical Prognostic Factor.J Korean Med Sci,2006,21(3):397-405.
[13]张莉娟.NHL血清LDH及β2微球蛋白测定的临床意义[J].临床血液学杂志,2004,128-129.
[14]刘劲 肖佩玲.乳酸脱氢酶测定对非霍奇金淋巴瘤的临床意义[J],医学临床研究,2009,26(2):310-311.
[15]Berggard I,Bearn AC.Isolation and properties of low molecular weight β_2-microglobulin occuring in human biological fluids.J Biol Chem,1968,243:4095.
[16]Schluter C,Duchrow M,Wohlenberg C,et al.The cell proliferation-associated nuclear antigen of antibody Ki-67:A very large ubiquitous nuclear protein with numerous repeated element,representing a new kind of cell cycle-maintaining proteins J Cell Biol,1993,123:513.
[17]Padilla D,Cubo T,Villarejo P,Molecular profile of node-negative colorectal cancer of poor prognosis using immunohistochemical determination of p53,ki67,VEGF,and metallopmteinase-9[J].Rev Esp Enferm Dig,2007,99(7):424-425.
[18]Bura M,Seiwerth S,Vladika I,Possible Prognostic Significance of p53 and Ki67 in Inverted Sinonasal Papilloma[J].Coil Antrepol,2007 31(2):545-549.
[19]King BE.Chen C,Locker J,et al.Immunophenotypic and Genotypic Markers of Follicular Center Cell Neoplasia in Diffuse Large B-cell Lymphoma[J].Mod Pathol,2000,13:1219-1231.
[20]Barrans SL,O'Connor SJ,Evans PA,et al.Rearrangement of the BCL6 locus at 3q27 is an independent poor prognostic factor in nodal diffuse large B-cell lymphoma[J].Br J Haematol,2002,117:322-332.
[21]Lossos IS,Jones CD,Warnke R,et al.Expression of a single gene,BCL-6strongly predicts survival in patients with diffuse large B-cell lymphoma[J].Blood, 2001.98:945-951.
[22]Ree HJ,Yang WI,Kim CW,et al.Coexpression of Bcl-6 and CD10 in diffuse large B-cell lymphomas:significance of Bcl-6 expression patterns in identifying germinal center B-cel lymphoma[J].Hum Pathol,2001,32:954-962.
[23]许良中,等.现代恶性淋巴瘤病理学[M].上海:上海科学技术出版社,2002,21-115.
[24]菊池昌弘,等.最新恶性淋巴瘤图谱[M].北京:人民军医出版社,2006,173-183.
[25]Marcus R.Current treatment options in aggressive lymphoma[J].Leuk Lymphoma,2003,44 Suppl4:S15-27.
[26]Grulich AE,Wan X.B- cell stimulation and prolonged immune defi-ciency.Are rick factors for non-Hodgkin's lymphoma in people wish AIDS[J].AIDS,2000,14(2):133.
[27]Diebold J,Anderson JR,Armitage JO,et al.Diffuse large B-cell lymphoma:a clinicopathologic analysis of 444 cases classified according to the updated Kiel classification[J].Leuk Lymphoma,2002,43:97-104.
[28]Jaffe ES,Harris N L,,Stein H,et al.World Health Organization Classification of tumor:Pathology and Genetics of Tumors of Haematopoietic and Lymphoid Tissues[J].France:IARC Press.Lyon,2001,171.
[29]李陶等.弥漫大B细胞淋巴瘤诊治进展[J].癌症进展杂志.2006,4(5):384-390.
[30]陈晓琳,吴铭.非霍奇金淋巴瘤患者血清乳酸脱氢酶测定及临床意义[J].中国现代医学杂志,2007,17(2):489.
[31]Karlsson FA,Wibell L,Ervin PE.β2-Microglobulin in clinical medicine.Scand J Clin Lab Invest.1980.40:S27-S37.
[32]王振学,高玉芳,孙宝义.β2-MG RIA在恶性肿瘤诊断中的应用[J].放射免疫学杂志,1996,9(2):103-104.
[33]许晓倩,王健民.β2微球蛋白在恶性血液病中的临床意义[J].中华血液学杂志,2005,26(7):444-446.
[34]夏忠军,林桂真,黄仁魏,等.非霍奇金氏淋巴瘤患者血清B-2微球蛋白检测对预后的价值[J].癌症,2001,20(4):406-408.
[35]张文书,路名芝,等.弥漫大B细胞淋巴瘤的研究现状[J].赣南医学院学报,2006(2):134-137.
[36]Jaffe ES,Harris NL,Stein H,Vardiman JW,eds.World Health Organization classification of tumours.Pathology and genetics,tumours of haematopoietic and lymphoid tissues[M].Lyon:IARC Press,2001:171-187.
[37]Feller AG,Diebold J.Histopathology of nodal and extranodal non-Hodgkin'S lymphomas[M].Berlin:Springer.Vedag,2004:75-99.
[38]Spier CM,Grogan TM,Lippman SM,et al.The aberrancy Of immunophenotype and immunoglobulin status as indicators of prognosis in diffuse large cel lymphoma[J].Am J Pahol,1988.133:118-126.
[39]Amytage JO,Weisenburger DD.New approach to classifying Non-Hodgkins lymphoma:clinincal features of the major histologic subtypes.Non-Hodgkins Lymphoma Classification Projet[J].J Cli Oneol,1998,16:2780-2795.
[40]Colomo L,lopez-Guillermo A,Perales M,et al.Clinical impact of the diferentiation profile assessed by immunophenotyping in patients with diffuse large B-cell lymphoma[J].Blood,2003.101:78.
[41]A lizadeh AA,Eisen MB,Davis RE,et al.Distinct types of diffuse large B-cell lymphoma identified.gene expression profiling[J].Nature,2000,403(6769):503-511.
[42]Rosenwald ff,Wright G,Chan WC,et al.The use of molecular profiling to prodict survival after chemotherapy for difuse large B-cell lymphoma[J].N Engl J Med,2002,346(25):1937-1947.
[43]Ship MA,Ross KN,Tamayo P,et al.Diffuse large B-cell lymphoma outcome prediction by gene-expression profiling and superrised machine learning[J].Nat Med,2002,8(1):68-74.
[44]Rssi D,Gaidane G.Molecular heterogeneity of diffuse large B cell lymphoma:Implications for disease management and prognosis[J].Hematology,2002,7(4):239.
[45]Freedman DM,Cantor KP,Ward MH,et al.A case- control study of ni-trate in drinking water and non- Hodgkin's lymphoma in Minnesota[J].Arch Environ Health,2000,55(5):326.
[46]武永吉.淋巴瘤的分型、分期和治疗原则[J].中华内科杂志,1995,34(9):641.
[47]Kuratomi K,Yano H,Tsuneoka M,et al.Immunohistochemical expression of mina53 and ki67 proteins in human primary gingival squamous cell carcinoma.[J]Kurume Med,2007,53(3-4):71-78.
[48]Mielcarek-Kuchta D,Olofsson J,Golusinski W.p53,Ki67 and cyclin D1 as prognosticators of lymph node metastases in laryngeal carcinoma.[J]Eur Arch Otorhinolaryngol,2003,260(10):549-554.
[1]朱雄增.弥漫大B细胞淋巴瘤研究进展[J].临床与实验病理学杂志,2005,20(3):262-265.
[2]Jaffe ES,Harris NL,Stein H,Vardiman JW,eds.World Healthe Organization classification of tumours.Pathology and genetics,tumours of haematopoietic and lymphoid tissues[M].Lyon:IARC Press,2001:171-187.
[3]Feller AG,Diebold J.Histopathology of nodal and extranodal non-Hodgkin'S lymphomas[M].Berlin:Springer.Vedag,2004:75-99.
[4]Egelhard M,Brittinger G,Huhn D,et al.Subclassification of diffuse large B-cell lymphomas according to the Kiel classification:distinction of center blastic and immunoblastic lymphomas is a significant prognostic risk factor[J].Blood,1997,89:2291-2297.
[5]Delabie J,Vandenberghe E,Kennes C,et al.Histiocyterich B-cell lymphoma.A distinct clinicopathologic entity possibly related to lymphocyte predominant Hodghin's disease,paragranuloma Subtype[J].Am J Surg Pathol,1992,16:37-48.
[6]Harris NL,Jaffe ES,Stein H,et al.A revised European American classification of lymphoid neoplasm:approposal from the Intenational lymphoma Study Group[J].Blood,1994,84:1361-1392.
[7]Haralambieva E,Pulford KA,Lamant L,et al.Anaplastic large-cell lymphoma of B-cell phenotype are anaplastic lymphoma kinase(ALK) negative and belong to the spectrum of diffuse large B-cell lymphomas[J].Brit J Haematol,2000,109:584-591.
[8]Dupin N,Diss TL,Kellam P,et al.HHV-8 is associated with a plasmablastic variant of Castleman disease that is linked to HHV-8-positive plasmablastic lymphoma[J].Blood,2000,95:1406-1412.
[9]Colomo L,lopez-Guillermo A,Perales M,et al.Clinical impact of the diferentiation profile assessed by immunophenotyping in patients with diffuse large B-cell lymphoma[J].Blood,2003.101:78.
[10]Bmrrans SL,Carter I,Owen RG,et al.Germinal center phenotype and bcl-2expression combined with the international prognostic index improves patient risk. stratification in difuse large B-cell lymphoma[J].Blood,2002,99:1136.
[11]A lizadeh AA,Eisen MB,Davis RE,et al.Distinct types of diffuse large B-cell lymphoma identified.gene expression profiling.Nature,2000,403(6769):503-511.
[12]Rosenwald if,Wright G,Chan WC,et al.The use of molecular profiling to prodict survival after chemotherapy for difuse large B-cell lymphoma.N Engl J Med,2002,346(25):1937-1947.
[13]Ship MA,Ross KN,Tamayo P,et al.Diffuse large B-cell lymphoma outcome prediction by gene-expression profiling and superrised machine learning.Nat Med,2002,8(1):68-74.
[14]Rssi D,Gaidane G.Molecular heterogeneity of diffuse large B cell lymphoma:Implications for disease management and prognosis.Hematology,2002,7(4):239.
[15]Ogan A,Bagdi E,Munson P,Isaacson PG.CD10 and BCL-6 expression in paraffin sections of normal lymphoid tissue and B-cell lymphomas[J].Am J Surg Pathol.2000,24(6):846-852.
[16]Cattoretti G,Chang CC.Cechova K.et al.BCL-6 protein is expressed in germinal-center B cells[J].Blood,1995,86(1):45-53.
[17]Atkunam Y,WarnkeRA.Montgomery K,et al.Analysis of MUM1/IRF4protein expression using tissue microarrays and immunohistochemistry[J].Mod Pathol,2001,14(7):686-694.
[18]Yamaguchi M,Seto M,Okamoto M,et al,De novo CD5+ diffuse large B-cell lymphoma.A clinicopathologic study of 109 patients[J].Blood,2002,99:815-21.
[19]Miller T,Grogan T,Dahlberg S,et al.Prognostic significance of the Ki-67associated proliferatiove antigen in aggressive non-Heal gkin's lymphoma.A prospective southwest oncology group trial[J].Blood,1994,83:1460.
[20]Rantanen S,Monni O,Joensuu H,et al.Causes and consequences of bel-2overexpression in diffuse large B-cell lymphoma[J].Leu-kemia Lymphoma,2001,42:1089-1098.
[21]Adida C,Crotty PL,M cgrath,et al.Develomentally regulated ex-pression of the novel cancer anti-apoptosis gene survivin in hu-man and mouse differentiation[J].Am J Patho,1998,152(1):43-49.
[22]Calette Adida,Corinne Haioun,et al.prognostic significance of survivin expression in diffuse large B-cell lymphoma[J].Blood,2000,96:1921-1926.
[23]Ichikawa A,Knoshita T,Watanabe T,et al.Mutations of the p53 gene as a prognostic factor in aggressive B-cell lymphoma[J].N Engl JM ed,1997,337:529-534.
[24]Maartense E,KramerMHH,Le Cesse E,et al.Lack of prognostic significance of Bcl-2 and p53 protein overexpression in elderly patients with diffuse large B-cell lymphoma:results from a population-based non- hodgldn's lymphoma registry[J].Leukemia Lymphoma,2004,45:101-107.
[25]Lossos IS,Jones CD,Warnke R,et al.Expression of a single gene,Bcl-6,strongly predicts survival in patients with diffuse large B-cell Lymphoma[J].Blood,2001,98(4):945-951.
[26]HarrisNL,Jaffe ES,Stein H,et al.A revised European American classification of lymphoid neoplasm:a proposal from the InternationalLymphoma Study Group [J].Blood,1994,845:1361-1392.
[27]Korl AD,Gessie SL,Snijder S,et al.Primary extranodalnon-Hodgkin's lymphoma(NHL):the impact of altematived efinitions tested in the Comprehensive Cancer Centre West population-based NHL registry[J].Ann Oncol,2003,14(1):131-134.
[28]李哗雄.胃粘膜相关淋巴瘤[J].中华放射肿瘤学杂志,2004,13(2):138-142.
[29]邓家栋.邓家栋临床血液学[M].上海:上海科学技术出版社,2001.
[30]张莉娟.NHL血清LDH及β2微球蛋白测定的临床意义[J].临床血液学杂志,2004,128-129.
[31]刘劲 肖佩玲.乳酸脱氢酶测定对非霍奇金淋巴瘤的临床意义[J],医学临床研究,2009,26(2):310-311.
[32]Berggard I,Beam AC.Isolation and properties of low molecular weight β_2-microglobulin occuring in human biological fluids.J Biol Chem,1968,243:4095.
[33]许晓倩,王健民.β2微球蛋白在恶性血液病中的临床意义[J].中华血液学 杂志,2005,26(7):444-446.
[34]夏忠军,林桂真,黄仁魏,等.非霍奇金氏淋巴瘤患者血清B-2微球蛋白检测对预后的价值[J].癌症,2001,20(4):406-408.
[35]Whelan J,Davis C,Rule Set al.Fludarabine phosphate for the treatment of low-grade lymphoid malignancy[J].Br J Cancer 1991:64(1):120-130.
[36]李陶等.弥漫大B细胞淋巴瘤诊治进展[J].癌症进展杂志.2006,4(5):384-390.
[37]Pfreundschuh M,Trumper L,Kloess M,et al.Two-weekly or 3-weekly CHOP chemotherapy with or without etoposide for the treatment of elderly of the NHL-B2trial ofthe DSHNHL[J].Blood,2004.104:634.
[38]Coiffier B,Haioun C,Ketterer N,et al.Rituximab(anti-CD20 monoclonal antibody)for the treatments of patients with relapsing or refractory aggressive lymphoma:Amulticenterphase II study[J].Blood,1998,92(6):1927.
[39]Laurie HS.Jane D.et al.Introduction of combined CHOP plus rituximab therapy dramatically improved outcome of diffuse large B-cell lymphoma in british columbia[J].J Clin Oncol,2005.23:5027.
[40]Feugier P,et al.Long-term results of the R-CHOP study in the treatm ent of elderly patients with diffuse large B-cell lymphoma:A study by the Grouped'Etude des lymphomes del'Adulte[J].J Clin Oncol,2005,18:4117.
[2]Gatter KC,Wanke RA,Diffuse large B-cell lymphoma.In:Jaffe ES,Harris NL,Stein H,et al.WHO Classification of Tumors:Pathology and Genetics of Internationa[J].Agency for Research on Cancer(IARC) Press,2001.171-174.
[3]Jaffe ES,Harris NL,Stein H,et al.World Health Organization Classification of Tumours.Pathology and Genetics of Tumours of Haematopoietic and lymphoid tissues[M],IARC Press:Lyon,2001,111-235.
[4]Jafe ES,Harris NL,Stein H,et al.World Health Organization Classification of Tumors Pathology and Genetics:Tumors of Haematopoietic and Lymphoid Tissues[M].IARC Press:Lyon,2001:171-174.
[5]Amytage JO,Weisenburger DD.New approach to classifying non-Hodgkin's lymphona:clinical features of the major histologic sublypes.Non-Hodgkin's lymphona Classification profect[J].J clin Oncol,1998,16:2780-2795.
[6]Harris NL,Stein H,Coupland SE,et al.New approaches to lymphoma diagnosis[J].Hematology,2001(Am soc Hematol Educ Program),194-220.
[7]张莉,曹永清,符岭华,等.湖南省恶性淋巴瘤、白血病流行病学调查[J].中国现代医学杂志,1998,8(12):25.
[8]Holly EA,Gautam M,Bracci PM.Comparison of interviewed and non-interviewed non- Hodgkin's lymphoma(NHL)Patients in the San Francis-co Bay A rea[J].Ann Epidemiol,2002,12(6):419.
[9]Goldman,Bennett.西氏内科学[M].第21版.第5分册.世界图书出版公司,2005.223.
[10]Wilder KB,Rodriguez MA,Medeiros LJ,et al.International prognostic index-based outcomes for diffuse large B-cell lymphomas[J].Cancer,2002.94:3083-3088.
[11]Hans CP,Weisenburger D,Greiner T,Gascoyne R,Delabie J,Ott G.Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using microarray.Blood,2004,103(1):275-282.
[12]Young-Ha Oh,Chan-Kum Park.Prognostic Evaluation of Nodal Diffuse Large B cell lymphoma by Immunohistochemical Prognostic Factor.J Korean Med Sci,2006,21(3):397-405.
[13]张莉娟.NHL血清LDH及β2微球蛋白测定的临床意义[J].临床血液学杂志,2004,128-129.
[14]刘劲 肖佩玲.乳酸脱氢酶测定对非霍奇金淋巴瘤的临床意义[J],医学临床研究,2009,26(2):310-311.
[15]Berggard I,Bearn AC.Isolation and properties of low molecular weight β_2-microglobulin occuring in human biological fluids.J Biol Chem,1968,243:4095.
[16]Schluter C,Duchrow M,Wohlenberg C,et al.The cell proliferation-associated nuclear antigen of antibody Ki-67:A very large ubiquitous nuclear protein with numerous repeated element,representing a new kind of cell cycle-maintaining proteins J Cell Biol,1993,123:513.
[17]Padilla D,Cubo T,Villarejo P,Molecular profile of node-negative colorectal cancer of poor prognosis using immunohistochemical determination of p53,ki67,VEGF,and metallopmteinase-9[J].Rev Esp Enferm Dig,2007,99(7):424-425.
[18]Bura M,Seiwerth S,Vladika I,Possible Prognostic Significance of p53 and Ki67 in Inverted Sinonasal Papilloma[J].Coil Antrepol,2007 31(2):545-549.
[19]King BE.Chen C,Locker J,et al.Immunophenotypic and Genotypic Markers of Follicular Center Cell Neoplasia in Diffuse Large B-cell Lymphoma[J].Mod Pathol,2000,13:1219-1231.
[20]Barrans SL,O'Connor SJ,Evans PA,et al.Rearrangement of the BCL6 locus at 3q27 is an independent poor prognostic factor in nodal diffuse large B-cell lymphoma[J].Br J Haematol,2002,117:322-332.
[21]Lossos IS,Jones CD,Warnke R,et al.Expression of a single gene,BCL-6strongly predicts survival in patients with diffuse large B-cell lymphoma[J].Blood, 2001.98:945-951.
[22]Ree HJ,Yang WI,Kim CW,et al.Coexpression of Bcl-6 and CD10 in diffuse large B-cell lymphomas:significance of Bcl-6 expression patterns in identifying germinal center B-cel lymphoma[J].Hum Pathol,2001,32:954-962.
[23]许良中,等.现代恶性淋巴瘤病理学[M].上海:上海科学技术出版社,2002,21-115.
[24]菊池昌弘,等.最新恶性淋巴瘤图谱[M].北京:人民军医出版社,2006,173-183.
[25]Marcus R.Current treatment options in aggressive lymphoma[J].Leuk Lymphoma,2003,44 Suppl4:S15-27.
[26]Grulich AE,Wan X.B- cell stimulation and prolonged immune defi-ciency.Are rick factors for non-Hodgkin's lymphoma in people wish AIDS[J].AIDS,2000,14(2):133.
[27]Diebold J,Anderson JR,Armitage JO,et al.Diffuse large B-cell lymphoma:a clinicopathologic analysis of 444 cases classified according to the updated Kiel classification[J].Leuk Lymphoma,2002,43:97-104.
[28]Jaffe ES,Harris N L,,Stein H,et al.World Health Organization Classification of tumor:Pathology and Genetics of Tumors of Haematopoietic and Lymphoid Tissues[J].France:IARC Press.Lyon,2001,171.
[29]李陶等.弥漫大B细胞淋巴瘤诊治进展[J].癌症进展杂志.2006,4(5):384-390.
[30]陈晓琳,吴铭.非霍奇金淋巴瘤患者血清乳酸脱氢酶测定及临床意义[J].中国现代医学杂志,2007,17(2):489.
[31]Karlsson FA,Wibell L,Ervin PE.β2-Microglobulin in clinical medicine.Scand J Clin Lab Invest.1980.40:S27-S37.
[32]王振学,高玉芳,孙宝义.β2-MG RIA在恶性肿瘤诊断中的应用[J].放射免疫学杂志,1996,9(2):103-104.
[33]许晓倩,王健民.β2微球蛋白在恶性血液病中的临床意义[J].中华血液学杂志,2005,26(7):444-446.
[34]夏忠军,林桂真,黄仁魏,等.非霍奇金氏淋巴瘤患者血清B-2微球蛋白检测对预后的价值[J].癌症,2001,20(4):406-408.
[35]张文书,路名芝,等.弥漫大B细胞淋巴瘤的研究现状[J].赣南医学院学报,2006(2):134-137.
[36]Jaffe ES,Harris NL,Stein H,Vardiman JW,eds.World Health Organization classification of tumours.Pathology and genetics,tumours of haematopoietic and lymphoid tissues[M].Lyon:IARC Press,2001:171-187.
[37]Feller AG,Diebold J.Histopathology of nodal and extranodal non-Hodgkin'S lymphomas[M].Berlin:Springer.Vedag,2004:75-99.
[38]Spier CM,Grogan TM,Lippman SM,et al.The aberrancy Of immunophenotype and immunoglobulin status as indicators of prognosis in diffuse large cel lymphoma[J].Am J Pahol,1988.133:118-126.
[39]Amytage JO,Weisenburger DD.New approach to classifying Non-Hodgkins lymphoma:clinincal features of the major histologic subtypes.Non-Hodgkins Lymphoma Classification Projet[J].J Cli Oneol,1998,16:2780-2795.
[40]Colomo L,lopez-Guillermo A,Perales M,et al.Clinical impact of the diferentiation profile assessed by immunophenotyping in patients with diffuse large B-cell lymphoma[J].Blood,2003.101:78.
[41]A lizadeh AA,Eisen MB,Davis RE,et al.Distinct types of diffuse large B-cell lymphoma identified.gene expression profiling[J].Nature,2000,403(6769):503-511.
[42]Rosenwald ff,Wright G,Chan WC,et al.The use of molecular profiling to prodict survival after chemotherapy for difuse large B-cell lymphoma[J].N Engl J Med,2002,346(25):1937-1947.
[43]Ship MA,Ross KN,Tamayo P,et al.Diffuse large B-cell lymphoma outcome prediction by gene-expression profiling and superrised machine learning[J].Nat Med,2002,8(1):68-74.
[44]Rssi D,Gaidane G.Molecular heterogeneity of diffuse large B cell lymphoma:Implications for disease management and prognosis[J].Hematology,2002,7(4):239.
[45]Freedman DM,Cantor KP,Ward MH,et al.A case- control study of ni-trate in drinking water and non- Hodgkin's lymphoma in Minnesota[J].Arch Environ Health,2000,55(5):326.
[46]武永吉.淋巴瘤的分型、分期和治疗原则[J].中华内科杂志,1995,34(9):641.
[47]Kuratomi K,Yano H,Tsuneoka M,et al.Immunohistochemical expression of mina53 and ki67 proteins in human primary gingival squamous cell carcinoma.[J]Kurume Med,2007,53(3-4):71-78.
[48]Mielcarek-Kuchta D,Olofsson J,Golusinski W.p53,Ki67 and cyclin D1 as prognosticators of lymph node metastases in laryngeal carcinoma.[J]Eur Arch Otorhinolaryngol,2003,260(10):549-554.
[1]朱雄增.弥漫大B细胞淋巴瘤研究进展[J].临床与实验病理学杂志,2005,20(3):262-265.
[2]Jaffe ES,Harris NL,Stein H,Vardiman JW,eds.World Healthe Organization classification of tumours.Pathology and genetics,tumours of haematopoietic and lymphoid tissues[M].Lyon:IARC Press,2001:171-187.
[3]Feller AG,Diebold J.Histopathology of nodal and extranodal non-Hodgkin'S lymphomas[M].Berlin:Springer.Vedag,2004:75-99.
[4]Egelhard M,Brittinger G,Huhn D,et al.Subclassification of diffuse large B-cell lymphomas according to the Kiel classification:distinction of center blastic and immunoblastic lymphomas is a significant prognostic risk factor[J].Blood,1997,89:2291-2297.
[5]Delabie J,Vandenberghe E,Kennes C,et al.Histiocyterich B-cell lymphoma.A distinct clinicopathologic entity possibly related to lymphocyte predominant Hodghin's disease,paragranuloma Subtype[J].Am J Surg Pathol,1992,16:37-48.
[6]Harris NL,Jaffe ES,Stein H,et al.A revised European American classification of lymphoid neoplasm:approposal from the Intenational lymphoma Study Group[J].Blood,1994,84:1361-1392.
[7]Haralambieva E,Pulford KA,Lamant L,et al.Anaplastic large-cell lymphoma of B-cell phenotype are anaplastic lymphoma kinase(ALK) negative and belong to the spectrum of diffuse large B-cell lymphomas[J].Brit J Haematol,2000,109:584-591.
[8]Dupin N,Diss TL,Kellam P,et al.HHV-8 is associated with a plasmablastic variant of Castleman disease that is linked to HHV-8-positive plasmablastic lymphoma[J].Blood,2000,95:1406-1412.
[9]Colomo L,lopez-Guillermo A,Perales M,et al.Clinical impact of the diferentiation profile assessed by immunophenotyping in patients with diffuse large B-cell lymphoma[J].Blood,2003.101:78.
[10]Bmrrans SL,Carter I,Owen RG,et al.Germinal center phenotype and bcl-2expression combined with the international prognostic index improves patient risk. stratification in difuse large B-cell lymphoma[J].Blood,2002,99:1136.
[11]A lizadeh AA,Eisen MB,Davis RE,et al.Distinct types of diffuse large B-cell lymphoma identified.gene expression profiling.Nature,2000,403(6769):503-511.
[12]Rosenwald if,Wright G,Chan WC,et al.The use of molecular profiling to prodict survival after chemotherapy for difuse large B-cell lymphoma.N Engl J Med,2002,346(25):1937-1947.
[13]Ship MA,Ross KN,Tamayo P,et al.Diffuse large B-cell lymphoma outcome prediction by gene-expression profiling and superrised machine learning.Nat Med,2002,8(1):68-74.
[14]Rssi D,Gaidane G.Molecular heterogeneity of diffuse large B cell lymphoma:Implications for disease management and prognosis.Hematology,2002,7(4):239.
[15]Ogan A,Bagdi E,Munson P,Isaacson PG.CD10 and BCL-6 expression in paraffin sections of normal lymphoid tissue and B-cell lymphomas[J].Am J Surg Pathol.2000,24(6):846-852.
[16]Cattoretti G,Chang CC.Cechova K.et al.BCL-6 protein is expressed in germinal-center B cells[J].Blood,1995,86(1):45-53.
[17]Atkunam Y,WarnkeRA.Montgomery K,et al.Analysis of MUM1/IRF4protein expression using tissue microarrays and immunohistochemistry[J].Mod Pathol,2001,14(7):686-694.
[18]Yamaguchi M,Seto M,Okamoto M,et al,De novo CD5+ diffuse large B-cell lymphoma.A clinicopathologic study of 109 patients[J].Blood,2002,99:815-21.
[19]Miller T,Grogan T,Dahlberg S,et al.Prognostic significance of the Ki-67associated proliferatiove antigen in aggressive non-Heal gkin's lymphoma.A prospective southwest oncology group trial[J].Blood,1994,83:1460.
[20]Rantanen S,Monni O,Joensuu H,et al.Causes and consequences of bel-2overexpression in diffuse large B-cell lymphoma[J].Leu-kemia Lymphoma,2001,42:1089-1098.
[21]Adida C,Crotty PL,M cgrath,et al.Develomentally regulated ex-pression of the novel cancer anti-apoptosis gene survivin in hu-man and mouse differentiation[J].Am J Patho,1998,152(1):43-49.
[22]Calette Adida,Corinne Haioun,et al.prognostic significance of survivin expression in diffuse large B-cell lymphoma[J].Blood,2000,96:1921-1926.
[23]Ichikawa A,Knoshita T,Watanabe T,et al.Mutations of the p53 gene as a prognostic factor in aggressive B-cell lymphoma[J].N Engl JM ed,1997,337:529-534.
[24]Maartense E,KramerMHH,Le Cesse E,et al.Lack of prognostic significance of Bcl-2 and p53 protein overexpression in elderly patients with diffuse large B-cell lymphoma:results from a population-based non- hodgldn's lymphoma registry[J].Leukemia Lymphoma,2004,45:101-107.
[25]Lossos IS,Jones CD,Warnke R,et al.Expression of a single gene,Bcl-6,strongly predicts survival in patients with diffuse large B-cell Lymphoma[J].Blood,2001,98(4):945-951.
[26]HarrisNL,Jaffe ES,Stein H,et al.A revised European American classification of lymphoid neoplasm:a proposal from the InternationalLymphoma Study Group [J].Blood,1994,845:1361-1392.
[27]Korl AD,Gessie SL,Snijder S,et al.Primary extranodalnon-Hodgkin's lymphoma(NHL):the impact of altematived efinitions tested in the Comprehensive Cancer Centre West population-based NHL registry[J].Ann Oncol,2003,14(1):131-134.
[28]李哗雄.胃粘膜相关淋巴瘤[J].中华放射肿瘤学杂志,2004,13(2):138-142.
[29]邓家栋.邓家栋临床血液学[M].上海:上海科学技术出版社,2001.
[30]张莉娟.NHL血清LDH及β2微球蛋白测定的临床意义[J].临床血液学杂志,2004,128-129.
[31]刘劲 肖佩玲.乳酸脱氢酶测定对非霍奇金淋巴瘤的临床意义[J],医学临床研究,2009,26(2):310-311.
[32]Berggard I,Beam AC.Isolation and properties of low molecular weight β_2-microglobulin occuring in human biological fluids.J Biol Chem,1968,243:4095.
[33]许晓倩,王健民.β2微球蛋白在恶性血液病中的临床意义[J].中华血液学 杂志,2005,26(7):444-446.
[34]夏忠军,林桂真,黄仁魏,等.非霍奇金氏淋巴瘤患者血清B-2微球蛋白检测对预后的价值[J].癌症,2001,20(4):406-408.
[35]Whelan J,Davis C,Rule Set al.Fludarabine phosphate for the treatment of low-grade lymphoid malignancy[J].Br J Cancer 1991:64(1):120-130.
[36]李陶等.弥漫大B细胞淋巴瘤诊治进展[J].癌症进展杂志.2006,4(5):384-390.
[37]Pfreundschuh M,Trumper L,Kloess M,et al.Two-weekly or 3-weekly CHOP chemotherapy with or without etoposide for the treatment of elderly of the NHL-B2trial ofthe DSHNHL[J].Blood,2004.104:634.
[38]Coiffier B,Haioun C,Ketterer N,et al.Rituximab(anti-CD20 monoclonal antibody)for the treatments of patients with relapsing or refractory aggressive lymphoma:Amulticenterphase II study[J].Blood,1998,92(6):1927.
[39]Laurie HS.Jane D.et al.Introduction of combined CHOP plus rituximab therapy dramatically improved outcome of diffuse large B-cell lymphoma in british columbia[J].J Clin Oncol,2005.23:5027.
[40]Feugier P,et al.Long-term results of the R-CHOP study in the treatm ent of elderly patients with diffuse large B-cell lymphoma:A study by the Grouped'Etude des lymphomes del'Adulte[J].J Clin Oncol,2005,18:4117.