bcl-2蛋白对胃肠和结内弥漫性大B细胞淋巴瘤的预后意义

 目的 通过93例病例的临床病理学研究,探讨Bcl-2蛋白在原发胃肠道弥漫性大B细胞淋巴瘤(DLBCL)中的预后作用。 方法 收集北京大学医学部基础医学院病理系淋巴瘤研究室确诊为DLBCL,且用非利妥昔单抗化疗的患者93例。用免疫组织化学检测Bcl-2,CD10,Bcl-6,Mum-1表达情况。随访全部病人的治疗过程和预后。采用SAS 9.1统计学软件对所得资料行卡方检验、生存曲线分析及log-rank检验。 结果 原发于胃肠道弥漫性大B细胞淋巴瘤46例。Bcl-2(+)病例26例,完全缓解(CR)8例; Bcl-2(-)病例20例,完全缓解10例。 两者完全缓解率无显著性差异(χ2 检验,P= 0.1852),两组的生存时间也无显著性差异(Log-Rank检验,P=0.4663)。原发于淋巴结弥漫性大B细胞淋巴瘤47例。Bcl-2(+)病例30例,完全缓解8例; Bcl-2(-)病例17例,完全缓解10例。两者完全缓解率存在显著性差异(χ2 验验,P=0.0293),两组的生存时间也存在显著性差异(Log-Rank检验,P= 0.0470)。 结论 Bcl-2蛋白对原发淋巴结内DLBCL有预后提示意义,而在原发胃肠道DLBCL中无预后提示意义。     

bcl-2与bcl-6在弥漫性大B细胞淋巴瘤中表达的研究

 目的　从蛋白水平和基因水平研究bcl-2、bcl-6在弥漫性大B细胞淋巴瘤（DLBCL）的表达。方法　应用免疫组织化学EnVision法对73例DLBCL进行CD3、CD10、CD20、bcl-2、bcl-6、MUM-1的标记。应用荧光原位杂交（FISH）技术检测其中57例t（14;18）染色体异位bcl-2基因的异常情况和54例bcl-6基因所在的3q27染色体的断裂和扩增情况。结果　肿瘤细胞表达CD10、bcl-6、MUM-1、bcl-2的阳性率分别为15.1 %、38.4 %、71.2 % 、79.2 %。57例患者中16例（28.1 %）存在t（14;18）。bcl-2蛋白表达与免疫学亚型有相关性（P＝0.035）,t（14;18）与预后有相关性（P＝0.045）,t（14;18）与bcl-2蛋白表达无相关性（P＝0.710）。54例中3q27染色体断裂11例（20.4 %）,扩增14例（25.9 %）。bcl-6阳性表达较阴性者预后好（P＝0.041）。bcl-6与3q27断裂和扩增无相关性（均P＝1.000）。结论　bcl-2、bcl-6蛋白和基因表达是各自独立的事件,它们在DLBCL中的意义不同。bcl-2蛋白是与免疫学亚型相关的预后标志物,bcl-2阳性的GCB型预后较差;t（14;18）是独立预后事件,阳性者预后较差,对靶向治疗患者应检测t（14;18）;bcl-6蛋白的表达有助于DLBCL的预后判断,可作为独立的预后因子。3q27染色体断裂可能提示预后较差。     

非免疫缺陷相关性B细胞淋巴瘤中bcl-2与EB病毒的相互关系

目的探讨非免疫缺陷相关性B细胞淋巴瘤(BCL)中EB病毒(EBV)与bcl-2蛋白表达的关系.方法采用免疫组织化学(IHC)、原位杂交(ISH)技术,分别检测63例非免疫缺陷相关性BCL中的bcl-2、LMP-1蛋白以及EBV编码的核内小RNA(EBER1/2),并且对bcl-2、EBER1/2双阳性的病例进行双标记.结果63例中,bcl-2蛋白阳性49例(77.8%),其中42例(85.7%)呈高表达.EBER1/2阳性6例(9.5%).LMP-1阳性1例(1.6%).双标记显示2例喉部浆细胞性淋巴瘤均呈EBER1/2、bcl-2双阳性(其中1例LMP-1阳性).结论bcl-2蛋白的表达与非免疫缺陷相关性BCL密切相关;而EBV与非免疫缺陷相关性BCL的关系不大;EBV通过LMP-1诱导bcl-2蛋白的表达,在非免疫缺陷相关性BCL发病中的意义有限,可能与发生部位、组织学类型有关;bcl-2蛋白高表达可能有多种诱导机制参与.     

bcl-2与NF-κB／p65在弥漫性大B细胞淋巴瘤不同亚型中表达的意义

 目的　探讨bcl-2与NF-κB／p65蛋白在弥漫性大B细胞淋巴瘤（DLBCL）不同亚型中的表达及其意义。方法　用免疫组织化学方法检测DLBCL患者CD10、bcl-6、MUM-1蛋白的表达,以Hans等的分型原则将其划分为GCB和非GCB／ABC亚型,同时标记bcl-2与NF-κB／p65抗体,比较bcl-2与NF-κB／p65蛋白在GCB和ABC亚型中的表达情况并分析二者与DLBCL两种主要亚型生存率的相关性。结果　bcl-2与NF-κB／p65蛋白在DLBCL中的表达率为67.1 %和77.1 %, 二者表达呈正相关;GCB亚型中bcl-2与NF-κB／p65的表达率分别为52.0 %和56.0 %,ABC亚型中bcl-2与NF-κB／p65蛋白的表达率分别为75.6 %和88.9 %,ABC亚型中bcl-2与NF-κB／p65的表达率高于GCB亚型;在GCB亚型中,bcl-2与NF-κB／p65蛋白的表达与总生存率无显著的相关性,而在ABC亚型DLBCL中,bcl-2与NF-κB／p65蛋白的表达与生存率密切相关。结论　仅在ABC亚型DLBCL中,bcl-2与NF-κB／p65蛋白的表达是影响预后的重要不利因素,因此,需在DLBCL亚分型的基础上评估bcl-2与NF-κB／p65蛋白表达的预后意义。     

弥漫性大B细胞淋巴瘤变型的病理及免疫表型分析

目的:探究弥漫性大B细胞淋巴瘤(DLBCL)变型的组织学特点及免疫表型。方法:收集108例DLBCL,总结其临床资料和组织病理学特点,进行组织微阵列免疫组化检测CD10、bcl-6的表达。结果:中心母细胞型(CB)为89.8%,免疫母细胞型(IB)2.8%,间变性大B细胞型(ALCL)1.9%,富于T细胞的B细胞型(TCRBCL)1.9%,其它变型3.7%;23.1%见较多背景反应细胞,41.7%伴有纤维化基质,21.3%有浆细胞分化,14.8%血管丰富、含有成片印戒样细胞,8.3%见坏死,3.7%见嗜酸细胞、硬化带。CB中44.2?10、48.1?l-6阳性,2例ALCL均阳性,而3例IB均阴性。结论:各变型有B细胞淋巴瘤共有的病理组织学特点,又有其各自的病理特征;CD10/bCL-6表达在识别变型中有重要意义。     

弥漫大B细胞性淋巴瘤分子亚型的蛋白表达研究

目的：在蛋白水平上研究国人弥漫性大B细胞淋巴瘤（diffuse large B-cell lymphoma,DLBCL）分子分型的蛋白表型特点,为DLBCL的病理诊断、预后和治疗提供依据。方法：取DLBCL标本52例行HE染色和免疫组化染色。在形态学分型的基础上,利用CD10、MUM1和bcl-6免疫标记对DLBCL进行分子分型,分为生发中心样B细胞样组（germi-nal center B-cell-like,GCB）和非生发中心样B细胞样组（non-germinal center B-cell-like,non-GCB）,分析其在DLBCL中的构成比,及CD10、MUM1和bcl-6的表达情况。结果：本组DLBCL中,non-GCB的构成比超过GCB（69.2%/30.8%）;统计学分析表明,GCB组间CD10、bcl-6、CD10/bcl-6的表达率的差异有显著性意义,其中CD10的表达率最高,bcl-6其次,CD10/bcl-6最低;non-GCB组间MUM1、MUM1/bcl-6的表达率的差异有显著性意义。结论：我国的DLBCL多起源于后生发中心B细胞,以non-GCB为主,预后较差。DLBCL在CD10、MUM1和bcl-6表达的差异对判定GCB组和non-GCB组有意义。     

韦氏环淋巴瘤中bcl-2、p53表达与预后的关系

目的以44例原发于韦氏环的B细胞中度恶性淋巴瘤作为对象，探讨bcl-2、p53阳性表达与预后的关系。方法22例韦氏环B细胞淋巴瘤患者蜡块，采用免疫组化S—P法染色，以细胞核着色计数分为阴性、阳性、强阳性。结果bcl-2阳性率59％，p53阳性表达率45％，bcl-2阳性表达组较其阴性表达组生存率低，有统计学意义，p53阳性表达组与阴性表达组比较其生存率未见统计学差异。结论临床上检测bcl-2蛋白表达可作为判断韦氏环B细胞、中度恶性淋巴瘤预后因子的指标。     

CD44v6、bcl-2和VEGF在子宫内膜腺癌中的表达及其意义

背景与目的:子宫内膜癌的发病机理至今尚未完全阐明,本研究拟探讨CD44v6、bcl-2、血管内皮生长因子(vascularendothelialgrowthfactor,VEGF)在子宫内膜腺癌发生、发展中的作用。方法:运用免疫组化技术SP法检测CD44v6、bcl-2、VEGF在55例子宫内膜腺癌及10例正常增生期子宫内膜、10例子宫内膜单纯性增生和10例不典型增生组织中的表达情况。结果:(1)在正常增生期子宫内膜、单纯性增生、不典型增生、子宫内膜腺癌中CD44v6及VEGF的阳性表达率分别为10.00%、40.00%、60.00%、78.18%和0%、0%、10.00%、83.84%,均有显著性差异(P<0.001,P<0.001),而bcl-2表达无显著差异;(2)55例子宫内膜腺癌组织中,CD44v6表达强度与手术分期及淋巴结有无转移呈负相关(P<0.05,P<0.01)bcl-2的表达强度在子宫内膜腺癌中与分化程度显著相关VEGF的表达强度与手术分期、肌层浸润、淋巴结有无转移显著相关;(3)bcl-2与VEGF、CD44v6在子宫内膜腺癌中有协同表达(P<0.05,P<0.05);(4)单因素生存分析CD44v及bcl-2与子宫内膜腺癌患者预后有关(P<0.01,P<0.05)多因素Cox模型分析筛选出患者的年龄、手术分期和CD44v是独立的预后影响因素,CD44v6阴性表达者的生存时间较阳性表达者短。结论:CD44v6、VEGF及bcl-2在子宫内膜腺癌的发生、发展过程中起不     

弥漫大B细胞淋巴瘤myc、bcl-2和bcl-6蛋白表达与基因异常的相关性研究

目的 探讨多重基因异常在弥漫大B细胞淋巴瘤(DLBCL)中的发生情况及其与蛋白高表达之间的关系.方法 收集2012年1月至2016年12月确诊的DLBCL非特指型患者50例,采用免疫组织化学法检测c-myc、bcl-2及bcl-6蛋白表达情况,采用间期荧光原位杂交(I-FISH)方法检测3个基因异常情况.结果 50例DLBCL患者中,男性27例,女性23例;年龄3~85岁,中位年龄50岁.发病部位:淋巴结23例(46.00%),结外27例(54.00%),以胃肠道最为多见(13例,48.15%).免疫组织化学检测c-myc蛋白阳性率94.00%(47/50),阳性细胞超过40%者41例(82.00%);bcl-2蛋白阳性率84.00%(42/50),阳性细胞超过70%者38例(76.00%);18例(36.00%)同时高表达c-myc和bcl-2.FISH检测结果显示,7例(14.00%)c-myc断裂,2例(4.00%)扩增;6例(12.00%)bcl-2断裂,4例(8.00%)扩增;8例(16.00%)bcl-6断裂,3例(6.00%)扩增,1例(2.00%)同时断裂及扩增;4例(8.00%)检测到多重基因异常,其中1例(2.00%)c-myc合并bcl-2基因异常,2例(4.00%)c-myc合并bcl-6基因异常,为双重打击淋巴瘤(DHL),1例(2.00%)同时检测到c-myc、bcl-2及bcl-6基因异常,为三重打击淋巴瘤(THL).4例多重基因异常病例中,3例起源于生发中心B细胞(GCB),1例起源于非GCB.18例c-myc和bcl-2蛋白双高表达组仅有3例(16.67%)检测到多重基因异常,包括2例DHL和1例THL.结论 多重基因异常在DLBCL中的检出率为8.00%.基因异常与蛋白高表达之间无明显相关性,DHL的检出依赖于分子遗传学检测.     

弥漫性大B细胞淋巴瘤中Bcl-2基因重排与蛋白表达的关系探讨

目的 探讨Bcl-2在弥漫性大B细胞淋巴瘤(diffuse large B-cell lymphoma,DLBCL)不同类型中的表达及意义。方法 应用免疫组织化学S-P法检测60例弥漫性大B细胞淋巴瘤标本中Bcl-2蛋白的表达水平;同时行RT-PCR检测外周血Bcl-2/IgH的表达水平。结果 60例DLBCL中,Bcl-2阳性率分别为61.67%(37/60);Bcl-2/IgH的阳性表达12例(12/60)。结论 Bcl-2有望成为DLBCL亚分类的指标。     

Quantitative analysis of bcl-2 expression in normal and leukemic human B-cell differentiation.

Lack of apoptosis has been linked to prolonged survival of malignant B cells expressing bcl-2. The aim of the present study was to analyze the amount of bcl-2 protein expressed along normal human B-cell maturation and to establish the frequency of aberrant bcl-2 expression in B-cell malignancies. In normal bone marrow (n=11), bcl-2 expression obtained by quantitative multiparametric flow cytometry was highly variable: very low in both CD34(+) and CD34(-) B-cell precursors, high in mature B-lymphocytes and very high in plasma cells. Bcl-2 expression of mature B-lymphocytes from peripheral blood (n=10), spleen (n=8) and lymph node (n=5) was significantly higher (P<0.02) in CD23(-) as compared to CD23(+) B cells, independent of the type of tissue analyzed. Upon comparison with normal human B-cell maturation, bcl-2 expression in neoplastic B cells from 144 patients was found to be aberrant in 66% of the cases, usually corresponding to bcl-2 overexpression (63%). Follicular lymphoma (FL) carrying t(14;18) and MALT lymphoma were the only diagnostic groups constantly showing overexpression of bcl-2. Bcl-2 overexpression was also frequently found in precursor B-acute lymphoblastic leukemia (84%), typical (77%) and atypical (75%) B-cell chronic lymphocytic leukemia, prolymphocytic leukemia (two of three cases), mantle cell lymphoma (55%), but not in t(14;18)(-) FL, splenic marginal zone lymphoma, Burkitt lymphoma and multiple myeloma.     

Paraffin Immunoreactivity of CD10, CDw75, and Bcl-6 in Follicle Center Cell Lymphoma

Follicle center cell lymphoma(FCCL) has the following immunophenotype(IP): sIg+, Pan B+, CD10+/-, CD5-, CD23-/+, CD43-, CD11c-, CD25-. In addition, reactivities of a malignant lymphoma with CDw75(LN-1) and bcl-6 are considered indicators of FCCL. Bcl-6 expression is common in Grade 1 FCCL (100%) and rare in other indolent B-cell lymphomas(BCL). In contrast, bcl-2 expression is common in FCCL (80%) and in other BCL subtypes. Since no previous study has correlated paraffin immunoreactivity(PIR) of CD10, CDw75, and bcl-6 in FCCL (Grades 1-3), this is this study's purpose.

Twenty-nine FCCL's were identified and reviewed (6, Grade 1; 10, Grade 2; 13, Grade 3) from the Division of Hematopathology, St. Louis University. The diagnoses were based on morphology and immunohistochemistry(IH)(21 cases) +/-the flow cytometric IP(14 cases). The paraffin blocks were stained for CD10 (Novacastra, Vector Laboratories, Burlingame, CA), CDw75 and bcl-6 (DAKO Corporation, Carpinteria, CA). Results showed that, CD10 by paraffin IH(PIH) was positive in 23 [18(strong); 3(moderate); 2(weak)] and negative in 6(3, Grade 2; 3, Grade 3). All CD10-cases were CDw75+; 4, bcl-6+. The two CD10-, bcl-6-cases were Grade 2. CDw75 was positive in 28 cases [16(strong); 11 (moderate); l(weak)] and negative in 1 (Grade 3; CD10+, bcl-2+, bcl-6+). Bcl-6 was positive in 26 [16(strong); 6(moderate); 4(weak)] and negative in 3(Grade 2's). Thus, the sensitivity of CD10, CDw75, and bcl-6 by PIH for FCCL was 79%, 97%, and 90%, respectively. Of the three stains evaluated by PIH in FCCL, CDw75 was the most sensitive, closely followed by bcl-6. CD10 was least sensitive-79%. By combining these 3 stains, the sensitivity was 100%; thus, a combined approach is recommended.     

bcl-6和Ki-67在弥漫大B细胞淋巴瘤中的表达及其意义

 【摘要】 目的 研究bcl-6和Ki-67在弥漫大B细胞淋巴瘤（DLBCL）中的表达及其临床意义。方法 应用免疫组织化学方法检测90例DLBCL标本中bcl-6和Ki-67的表达情况。以20例淋巴结反应性增生（RH）标本作为对照。结果 bcl-6在DLBCL组织中阳性表达率为54.44 %（49／90）, 在RH组织中为15.00 %（3／20）,两者差异有统计学意义（χ2＝10.214,P＝0.001）;其表达与临床分期、乳酸脱氢酶水平、B症状及Hans分型相关 (χ2值分别为5.257、5.257、4.704、16.024,均P＜0.05)。Ki-67在DLBCL组织中的高表达率为80.00 %（72／90）,而在RH组织中为20.00 %（4／20）,两者差异有统计学意义（χ2＝27.585,P＝0.000）,其表达与临床分期、国际预后指数（IPI）及近期疗效相关（χ2值分别为5.889、6.451、6.024,均P＜0.05)。结论　bcl-6和Ki-67的异常表达与DLBCL的临床分期、IPI及Hans分型等相关,可为其临床治疗及预后判断等提供参考依据。     

The expression of IgM is helpful in the differentiation of primary cutaneous diffuse large B cell lymphoma and follicle center lymphoma

Diffuse large B-cell infiltration of the skin includes mainly primary cutaneous follicle center lymphoma (PCFCL) with diffuse architecture and diffuse large B cell lymphoma (PCDLBCL), leg type. Differentiation of these lymphomas on morphology may be troublesome. Immunohistochemistry panel, including CD20, CD79a, bcl-6, bcl-2, MUM-1, FOX-P1 is mandatory. However, in minority of cases, these markers would not suffice. In order to search the value of another marker, IgM, 30 cases of PCFCL and 10 cases of PCDLBCL, leg type were included in the study. As suggested in a recent literature, our study denoted that expression of IgM was useful as an additional tool for differentiation.     

Rearrangement of immunoglobulin, T-cell receptor, and bcl-2 genes in malignant lymphomas in Hong Kong

The pattern of malignant lymphomas in the Hong Kong Chinese population is characterized by a low incidence of Hodgkin's disease and follicular lymphomas. The authors studied the immunoglobulin (Ig), T-cell receptor (TCR), and bcl-2 gene rearrangement in 62 cases of malignant lymphoma in this population by Southern blot hybridization. Two cases of Hodgkin's disease showed no rearrangement of the Ig and TCR genes. All 42 cases of B-cell lymphoma had Ig heavy chain (JH) rearrangement with or without additional rearrangement of the light chains (C kappa and C lambda). One case of diffuse B-cell lymphoma had additional T-cell receptor beta-chain (C beta) rearrangement. Sixteen of 18 cases of T-cell lymphoma had C beta rearrangement, and one case of T-lymphoblastic lymphoma had additional JH rearrangement. Two of eight (25%) cases of follicular lymphoma but only one of the 34 (2.9%) cases of diffuse B-cell lymphoma had bcl-2 rearrangement that was detected by pFL-1 probe. None of the 62 cases showed bcl-2 rearrangement using the pFL-2 probe. In conclusion, the Ig and TCR gene rearrangement pattern of the lymphomas found in Hong Kong correlates well with the T-cell and B-cell lineage, which is similar to reports in the white population. However, the incidence of bcl-2 gene rearrangement in follicular B-cell lymphoma is lower than that reported in the US but comparable with that in Japan.