不同类型淋巴瘤Survivin的表达及其意义

背景与目的:淋巴瘤的诊断与分型是临床病理诊断的难点。本研究检测抗凋亡基因survivin在不同类型淋巴瘤中的表达,并探讨其对淋巴瘤分型的意义。方法:用免疫组化法检测83例淋巴瘤、5例淋巴结反应性增生石蜡标本中survivin蛋白的表达;同时用RT-PCR检测K562、HL-60、Raji、Jurkat细胞系和以上病例中18例淋巴瘤及2例淋巴结反应性增生新鲜标本中survivinmRNA的表达;对不同类型的淋巴瘤survivin蛋白及mRNA表达进行半定量分析。结果:Survivin蛋白在非霍奇金淋巴瘤(non-Hodgkinslymphoma,NHL)的DLBL(diffuselargeBcelllymphoma)、BL(Burkittlymphoma)、LBL(lymphoblasticlymphoma)中有较高的表达,分别为87.2%(34/39)、100%(2/2)、85.7%(6/7),而在FL(follicularlymphoma)、MALT(extranodalmarginalzoneB-celllymphomaofmucosa-associatedlymphoidtissue)和MZL(marginalzonelymphoma)中表达较低,分别为22.2%、33.3%和40.0%,且多为弱阳性。高表达组(DLBL、BL、LBL)与低表达组(FL、MZL、MALT)之间差异有统计学意义(P<0.01)。并且DLBL中survivin阳性者中位年龄为57岁,明显高于阴性者41岁。霍奇金淋巴瘤(Hodgkinslymphoma,HL)中大部分R-S(Reed-Sternberg)细胞表达survivin蛋白。NHL中survivinmRNA的检测结果与其蛋白水     

不同类型淋巴瘤Survivin的表达及其意义(英文)

目的淋巴瘤的诊断与分型是临床病理诊断的难点。本研究检测抗凋亡基因 survivin 在不同类型淋巴瘤中的表达,并探讨其对淋巴瘤分型的意义。方法用免疫组化法检测中山大学附属一院及肿瘤医院2001年1月～2003年6月219例淋巴瘤、13例淋巴结反应性增生石蜡标本中 survivin 基因的表达;同时用 RT-PCR 检测 K562、HL60、Raji、Jurkat 细胞系和以上病例中18例淋巴瘤及2例淋巴结反应性增生新鲜标本中 survivin mRNA 的表达;对不同类型的淋巴瘤 survivin 蛋白及 mRNA 表达的结果进行半定量分析。结果 Survivin 蛋白在非霍奇金淋巴瘤(NHL)的弥漫性大 B 细胞性淋巴瘤(DLBL)(88.6%,70/79)、伯基特淋巴瘤(BL)(100%,2/2)、淋巴母细胞淋巴瘤(LBL)(92.3%,12/13)中有较高的表达,而在滤泡性淋巴瘤(FL)(18.2%),粘膜相关性结外边缘带 B 细胞淋巴瘤(MAL-oma)(40.9%)和 MZL(marginal zone lymphoma)(33.3%)中表达较低,且多为弱阳性。高表达组(DLBL、BL、LBL)与低表达组(FL、MZL、MALT)之间差异有统计学意义,X~2检验,P<0.01。霍奇金淋巴瘤(HL)中大部分 R-S(Reed-Sternberg)细胞表达 survivin 蛋白。NHL 中 survivin mRNA 的检测结果与其蛋白水平的表达呈正相关(相关系数 r=0.6270,P<0.01)。结论 survivin 蛋白及 mRNA 表达水平在不同类型淋巴瘤存在着明显的差异,survivin 可能作为一个分子标记对淋巴瘤分型具有一定的价值。     

非霍奇金淋巴瘤survivin和Ki67的表达及意义

 目的　探讨survivin蛋白、增殖相关抗原Ki 67在不同恶性度非霍奇金氏淋巴瘤 (NHL)中的表达及意义。方法　应用免疫组织化学envisionsystem法检测NHL组织中survivin蛋白和Ki 67的表达。结果　在反应性增生淋巴组织 (LNRH)中未检测到survivin蛋白表达。在NHL中survivin蛋白表达率为 51.9% (2 8/ 54) ,其中低度恶性及中高度恶性组NHL中的表达率分别为 19% (4/ 2 1)、72 .7% (2 4/3 3 ) ,两组之间比较差异有显著性 (P <0 .0 0 1)。survivin、Ki67表达与恶性度均显著相关 ,而且survivin表达也与Ki67指数相关。结论　survivin蛋白在NHL患者组织中高表达 ,并可能通过其抗凋亡功能参与NHL发生发展     

B细胞性非霍奇金淋巴瘤中BCL-6、CD10和BCL-2的蛋白表达及其临床病理意义

背景与目的：BCL-6、CD10均为淋巴结生发中心B淋巴细胞（GC—B细胞）的标志，它们在结内外弥漫性大B细胞淋巴瘤（DLBCL）及其它类型淋巴瘤中的表达特征及意义值得研究。本研究分析了B细胞性非霍奇金淋巴瘤（B—NHL）中BCL-6、CD10和BCL-2的蛋白表达及其临床病理意义。方法：免疫组化EnVision两步法分析135例B—NHL常见类型[包括DLBCL 22例，滤泡性淋巴瘤（FL）18例，B小淋巴细胞性淋巴瘤（B—SLL）18例，套细胞淋巴瘤（MCL）15例，淋巴浆细胞性淋巴瘤（LPL）7例，Burkitt’s淋巴瘤（BL）5例，B淋巴母细胞性淋巴瘤（LBL）3例；结外DLBCL 29例，胃粘膜相关淋巴样组织结外边缘区B细胞淋巴瘤（MALT-L）18例]和对照组5例T—NHL、5例结节型淋巴细胞为主型霍奇金淋巴瘤（NLPHL）以及10例淋巴结反应性增生（RLH）石蜡包埋组织中BCL-6、CD10以及BCL-2蛋白的表达。结果：①BCL-6和CD10阳性表达均只见于RLH（100％和100％）、结内DLBCL（72．7％和40．9％）、结外DLBCL（75．9％和41.4％）、FL（88．9％和72．2％）以及BL（100％和100％），其余B—NHL如B-SLL、MCL、MALT—L、LPL、LBL以及T-NHL和NLPHL中均未见BCL-6和CD10蛋白的表达。BCL-2蛋白表达可见于结内、结外DLBCL、FL、B—SLL、MCL、MALT—L以及LBL，阳性率分别为：36．4％、27．6％、83．3％、88．9％、86．7％、72．7％和33．3％；而LPL、BL、T—NHL以及NLPHL未见BCL-2蛋白表达；②DLBCL中BCL-6的表达形式可以分为四种类型：GC／FL型、中间型、散在型和阴性型；③40．9％的结内DLBCL、41．4％的结外DLBCL、72．2％的FL以及100％的BL为BCL-6＋／CD10＋表达，其中BCL-6蛋白表达均为GC／FL型；④在临床特征上，BCL-6＋／CD10＋的结内DLBCL与非BCL-6＋／CD10＋的结内DLBCL相比，前者的临床分期低于后者（P〈0．05）。结论：BCL-6、CD10和BCL-2蛋白的联合检测，可以用于部分B—NHL的诊断和鉴别诊断；BCL-6＋／CD10＋的结内淋巴瘤可能具有更好的临床预后。     

NF-κB、c-myc和survivin在非霍奇金淋巴瘤中的表达及临床意义

目的:探讨非霍奇金淋巴瘤(non-Hodgkin's lymphoma,NHL)中NF-κB、c-myc和survivin蛋白表达水平及其临床意义.方法:采用免疫组织化学PV-9000二步法检测62例NHL肿瘤组织及18例淋巴结反应性增生(reactive hyperplasia of lymph node, RH)组织中NF-κB、c-myc和survivin的表达情况,并分析蛋白表达与临床病理特征、化疗疗效及预后的相关性.结果:NF-κB、c-myc和survivin蛋白在NHL组织中的阳性表达率分别为61.29%、77.42%和72.58%,高于RH组织中的表达率16.67%、 22.22%和11.11%(P<0.01).NF-κB、c-myc和survivin的表达与NHL的恶性程度、临床分期均呈正相关(P<0.05),而与患者的年龄、全身症状、PS评分和淋巴结外病变数目均无相关性(P>0.05),其中NF-κB、c-myc在T细胞淋巴瘤中的阳性表达率高于B细胞淋巴瘤(P<0.05).NF-κB、c-myc和survivin在NHL组织中阳性表达率与其化疗疗效呈负相关(r=-0.362、r=-0.296和r=-0.273,P<0.05).NHL组织中NF-κB、c-myc和survivin表达之间均存在正相关关系(r=0.514、r=0.476和r=0.313,P<0.05),且NF-κB和c-myc在国际预后指数(international prognostic index,IPI)高危组中的表达均高于IPI低危组(P<0.05).结论:NF-κB、c-myc和survivin的表达状况与NHL患者恶性程度、临床分期及化疗疗效存在相关性,可作为评价NHL患者预后的生物学参考指标.     

B细胞淋巴瘤中Fas和FasL蛋白的表达及其意义

背景与目的:以往研究表明,Fas/FasL是细胞凋亡的诱导基因,有许多肿瘤的发生都与Fas/FasL功能失调及表达异常有关,本研究旨在通过对淋巴瘤及良性淋巴组织中Fas/FasL基因蛋白表达规律的研究,为诊断淋巴瘤提供新的观察指标及实验依据。方法:对确诊的92例B细胞淋巴瘤石蜡标本及20例良性淋巴组织石蜡标本用免疫组化方法进行Fas和FasL蛋白表达的检测。结果:Fas主要表达在细胞膜上。FasL主要表达在细胞浆,部分表达在细胞核。B细胞淋巴瘤中Fas蛋白总阳性率为66.3%,FasL蛋白总阳性率为67.4%,良性淋巴组织中Fas及FasL蛋白表达阳性率均为60.0%。淋巴瘤组织与良性淋巴组织之间Fas及FasL蛋白表达差异无显著性(P>0.05)。但阳性细胞在良恶性淋巴组织之间分布部位不同。淋巴瘤各亚组之间Fas及FasL蛋白表达差异有显著性(P<0.05)。Fas蛋白表达在弥漫大B细胞淋巴瘤(diffuselargeB-celllymphoma,DLBL)(87.2%)高于滤泡细胞淋巴瘤(follicularlymphoma,FL)(64.5%)及小细胞淋巴瘤(smallcelllymphoma,SLL)(31.8%);FasL蛋白表达在DLBL(89.7%)高于FL(67.7%)及SLL(27.3%)。Fas及FasL的蛋白表达与性别、年龄、部位无关。结论:Fas及FasL的阳性率不能作为鉴别B细胞淋巴瘤良恶性的指标,而Fas和FasL在良恶性细胞中分布部位不同可做为参考     

蛋白质芯片技术在B细胞淋巴瘤病理分型及预后方面的应用

 目的　应用表面增强激光解吸／离子化-飞行时间-质谱（SELDI-TOF-MS）蛋白质芯片技术检测B细胞非霍奇金淋巴瘤（B-cell NHL）及其弥漫大B细胞淋巴瘤（DLBCL）和滤泡性淋巴瘤（FL）患者血清中的差异表达蛋白,探讨其临床意义。方法　弱阳离子交换蛋白芯片检测54例初治B-cell NHL和27名健康人血清中的差异表达蛋白,并筛选DLBCL与FL之间病理类型的差异表达蛋白及影响DLBCL预后的差异表达蛋白。结果　B-cell NHL 患者血清中有5个特异性标志蛋白,高表达蛋白质的相对分子质量为7974和15 938,低表达的为3398、8564和8692。DLBCL与FL之间有3个差异表达蛋白,为3379、3976和4302,在DLBCL低表达,在FL高表达。影响DLBCL患者预后的差异表达蛋白有2个,为4795和4998,其高表达者预后好。结论　SELDI-TOF-MS蛋白质芯片技术可以直接筛选B-cell NHL血清中相对特异的标志蛋白作为诊断的指标,并用于病理分型、判断预后。     

survivin、环氧化酶-2及bcl-2在非霍奇金淋巴瘤中的表达及其相关性

 目的　研究survivin、环氧化酶-2（COX-2）及bcl-2在非霍奇金淋巴瘤（NHL）中的表达及其临床意义并初步探讨三者的相关性。方法　用免疫组织化学MaxVision法检测44例NHL和同期20例反应性淋巴样增生（RH）组织中survivin、COX-2及bcl-2蛋白的表达。结果　survivin、COX-2、bcl-2在NHL中的阳性表达率分别为70.45 %（31／44）、68.18 %（30／44）、63.64 %（28／44）;RH中分别为40.00 %（8／20）、40.00 %（8／20）和20.00 %（4／20）,差异有统计学意义（均P＜0.05）。NHL组织中,COX-2与survivin（r＝0.306,P＝0.043）、survivin与bcl-2（r＝0.339,P＝0.040）的表达均呈正相关。结论　COX-2、survivin、bcl-2在NHL组织中呈高表达;survivin、bcl-2作为分子标志可能对淋巴瘤的诊断、分型具有一定的价值;COX-2和survivin、survivin和bcl-2在NHL的发生和发展中可能具有协同作用。     

EB病毒感染与儿童淋巴瘤的相关性研究

目的 研究EB病毒(EBV)与儿童淋巴瘤的相关性.方法 选取我院1996至2005年间的石蜡包埋、淋巴结来源的36例霍奇金淋巴瘤(HL)和51例非霍奇金淋巴瘤(NHL)病理标本,以同期保存的45例淋巴结反应性增生(RL)病理标本为对照.采用免疫组化法检测EBV-LMP1,采用原位杂交法检测EBV-EBERS,判断EBV的阳性率.结果 HL的EBV阳性检出率为72.2%(26/36),NHL的EBV阳性检出率为15.7%(8/51),RL的EBV阳性检出率为33.3%(15/45),3组间EBV的阳性检出率差异有统计学意义(P=0.000).结论 儿童HL与EBV感染密切相关;儿童NHL的EBV阳性检出率较低,可能与其病理类型有关.     

非霍奇金淋巴瘤组织中突变型p53、bcl-2、Ki-67及survivin蛋白表达及临床意义

目的:探讨突变型p53、bcl-2、Ki-67、survivin在非霍奇金淋巴瘤(NHL)组织中的表达及其临床价值.方法:采用组织芯片技术及免疫组化SP法检测142例NHL和18例良性淋巴结病变组织中突变型p53、bcl-2、Ki-67、survivin蛋白的表达.结果:突变型p53、bcl-2、Ki-67、survivin蛋白在NHL中的表达阳性率分别为55.63%(79/142)、51.41%(73/142)、48.59%(69/142)和60.56%(86/142);与对照组相比具有非常显著性差异(P<0.01).在不同性别以及在不同细胞类别NHL中,突变型p53、bcl-2、Ki-67、survivin蛋白表达阳性率基本一致,统计分析无显著性差异(P>0.05);但在低年龄组、临床Ⅲ-Ⅳ期和高度恶性组突变型p53、bcl-2、Ki-67、survivin蛋白表达阳性率明显高于高年龄组、临床Ⅰ-Ⅱ期和低度恶性组,有显著性差异(P<0.05);突变型p53蛋白与Ki-67蛋白呈正相关(r=0.8769),survivin蛋白与bcl-2蛋白表达呈正相关(r=0.8846).结论:突变型p53、bcl-2、Ki-67、survivin蛋白在NHL组织中高表达,与NHL的发生与发展、细胞恶性程度和组织病理学等级密切相关.     

Survival of patients with marginal zone lymphoma

BACKGROUND.

Prognostic factors and outcomes in patients with marginal zone lymphoma (MZL) have been studied in small cohort studies, which may not reflect the population at large.

METHODS.

Clinical characteristics and survival outcomes of adult patients with MZL who were diagnosed between 1995 and 2009 were evaluated using the Surveillance, Epidemiology, and End Results (SEER) database. The authors generated clinical prognostic models for subtypes of MZL and compared survival during the periods of 1995 through 2000, 2001 through 2004, and 2005 through 2009.

RESULTS.

The prognosis was significantly better for patients with mucosa‐associated lymphoid tissue (MALT) lymphoma (5‐year relative survival rate of 88.7%; P < .0001) compared with those with the splenic MZL (SMLZ)or nodal MZL (NMZL) subtypes (5‐year relative survival rates of 79.7% and 76.5%, respectively). There was evidence of improved outcomes in patients with NMZL and MALT lymphomas between 1995 and 2009 (P < .0001), with no difference noted in patients with SMZL (P = .56). Advancing age and the presence of B symptoms had prognostic significance in all MZL subtypes. Male sex and stage of disease were significant only for the NMZL and MALT categories. Survival in patients with MALT lymphomas varied depending on the site of origin, with a worse prognosis noted in those with gastrointestinal and pulmonary locations of origin (5‐year incidence rate of lymphoma‐related death, 9.5%‐14.3%) compared with ocular, cutaneous, and endocrine sites (4.5%‐7.8%; P < .0001).

CONCLUSIONS.

The survival for patients with SMZL is similar to that for those with NMZL, and unlike the NMZL and MALT subtypes, it has not improved over the past decade. The prognosis of patients with MALT lymphoma varies according to the anatomical site of origin. Cancer 2013. © 2012 American Cancer Society.     

p27kip1 expression is inversely related to the grade of gastric MALT lymphoma

Background: Decreased or lost expression of the cyclin-dependent kinase inhibitor p27^kip1 protein has been found to be a poor prognostic factor in many cancers, including gastric cancer. Aim: To evaluate p27^kip1 expression in gastric mucosa-associated lymphoid tissue (MALT) and gastric B-cell lymphoma. Methods: Fifty-two cases of gastric lymphoma, mean age 68.7 yr (range 23–90 yr), 11 of chronic Helicobacter pylori-associated gastritis, and 5 of normal gastric mucosa were studied. Patients were classified into two groups. Stage IE gastric lymphomas were defined as local gastric lymphoma of MALT and more advanced stages as advanced gastric lymphoma. Twenty-three patients diagnosed as stage IE, 13 of these were low-grade and 10 diffuse large B-cell lymphoma (DLBL). Twenty-nine patients were at stage IIE or above, 18 with low-grade and 11 with DLBL. Serial sections were evaluated by immunohistochemistry after staining with antibodies against p27/Kip1 and Ki-67. Results: The proliferative index was higher in gastric DLBL than in low-grade MALT lymphomas, 57.1±31.2 vs 17.3±20.6 (p=0.0001). The mean p27^kip1 expression score for high-grade patients was significantly lower compared with that of low-grade patients, 0.5 ± 0.4 and 1.6±0.8, respectively (p=0.001). Comparative evaluation of p27^kip1 expression in malignant lymphoid cells revealed that B cells of the localized gastric DLBL patients expressed the least p27^kip1, 0.36±0.32. This value was lower than that of malignant lymphoid cells of patients with advanced DLBL, 0.64±0.53, advanced low-grade MALT lymphoma, 1.59±0.79, and localized low-grade MALT lymphoma, 1.59±0.84. In the multivariate model in which all p27^kip1 variables were entered, the expression of p27^kip1 in malignant lymphoid cells was inversely correlated with the grade of the lymphoma irrespective of the stage of the disease (p=0.0001), and significantly predicted grade: OR:0.07, 95% CI 0.07–0.31, p=0.0001. Conclusion: p27^kip1 may be a putative distinct molecular marker to differentiate between low-grade and high-grade gastric lymphoma.     

Management of marginal zone lymphomas

Opinion statement Marginal-zone lymphoma (MZL) includes three subtypes depending on the site of lymphoma involvement: extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma); splenic MZL; and nodal MZL. Although there is a common cell of origin and similarities concerning a possible chronic antigenic stimulation by microbial pathogens and/or auto-antigens, the clinical presentation is very different with symptoms related to lymphoma location. MALT and splenic MZL present with an indolent disease with good performance status, no B symptoms, and no adverse prognostic factors and are associated with long survival. Patients with nodal MZL present with a shorter progression-free survival. Clinical and biological prognostic factors identified in reported series are heterogeneous. The optimal treatment has yet to be defined for the three subtypes, and current strategies are described in this review.     

Subcutaneous ‘lipoma-like’ B-cell lymphoma associated with HCV infection: a new presentation of primary extranodal marginal zone B-cell lymphoma of MALT

BackgroundHepatitis C virus (HCV) infection has been linked to lymphoproliferative disorders. Marginal zone B-cell lymphoma (MZL) represents one of the most frequent lymphoma subtypes associated with HCV infection. We describe an unusual subset of HCV-associated MZL characterized by subcutaneous presentation.Materials and methodsA series of 12 HCV-positive patients presenting with subcutaneous nodules that revealed lymphoma infiltration at biopsy. Molecular analysis of immunoglobulin heavy chain (IGH) gene rearrangement and FISH investigations for t(11;18)(q21;q21) and t(14;18)(q32;q21) were carried out in nine patients.ResultsThe 12 patients (median age 69.5 years), all with positive HCV serology, presented with single or multiple subcutaneous nodules resembling lipomas. Histologically the lesions showed lymphoid infiltrates, consistent with extranodal MZL of mucosa-associated lymphoid tissue (MALT). Functional IGH gene rearrangements were identified in nine tested patients, with somatic mutations in 82%, indicating a histogenesis from germinal center-experienced B cells. The t(11;18) was found in two of nine cases. Staging did not show any other lymphoma localization. In two patients, a response was achieved with antiviral treatment. Extracutaneous spread to MALT sites occurred in a case.ConclusionsOur observations expand the spectrum of HCV-associated lymphomas to include a subset of extranodal MZL characterized by a novel primary ‘lipoma-like’ subcutaneous presentation and indolent clinical course.     

边缘区淋巴瘤研究进展

边缘区淋巴瘤（MZL）约占非霍奇金淋巴瘤的10%,可以分为黏膜相关淋巴组织（MALT）淋巴瘤、淋巴结MZL及脾脏MZL,其中以MALT淋巴瘤最为常见,约占非霍奇金淋巴瘤的7.5%。2016年第58届美国血液学会（ASH）年会关于MZL研究进展的报告涵盖从基础研究到临床诊疗多个方面：基于流式细胞学、细胞遗传学和荧光原位杂交（FISH）等技术对MZL的发病机制的研究进一步深入,新型预后指数系统的提出有助于对MZL患者分级并指导治疗,治疗方案的变化及新药的加入能够进一步提高此类患者的临床疗效和安全性。     

Marginal zone lymphoma

Marginal zone lymphomas (MZLs) comprise 3 distinct entities: extranodal MZL of mucosa-associated lymphoid tissue (MALT), splenic MZL, and nodal MZL. Gastric MALT lymphoma is the most common extranodal MZL and often develops as a result of chronic Helicobacter pylori gastritis. Such cases frequently respond to antibiotics directed against H. pylori. Antigen-driven lymphomatous disease can also be seen in the association of Borrelia burgdorferi with MALT lymphoma of the skin, Chlamydia psittaci with MALT lymphoma of the ocular adnexa, Campylobacter jejuni with immunoproliferative disease of the small intestine, and hepatitis C with splenic MZL. This article discusses the pathogenesis and clinical features of MZL and the treatment options available to patients.