B细胞特异性激活蛋白与CD20在淋巴组织增生性疾病中的表达

目的探讨B细胞特异性激活蛋白(B cell-specific activator protein, BSAP)在淋巴组织增生性疾病中表达情况及在淋巴瘤鉴别诊断中的意义.方法观察63例淋巴组织增生性疾病的组织病理学形态,按WHO新分类方案进行淋巴瘤分型,采用免疫组织化学S-P法同步检测比较BSAP和CD20的表达.结果 9例淋巴结反应性增生的B淋巴细胞,34例B细胞性淋巴瘤的瘤细胞均表达BSAP和CD20,但BSAP的中等到强阳性表达率(69.8%)高于CD20(53.5%),二者差异无显著性(P>0.05);6例霍奇金淋巴瘤H/RS瘤细胞表达阳性率为83.2%;14例T细胞淋巴瘤的肿瘤细胞均不表达BSAP.结论 BSAP表达定位于B淋巴细胞的核内,清晰易见,在B细胞性淋巴瘤表达多呈强阳性,可用于淋巴瘤的分型与鉴别诊断,是判断肿瘤为B细胞来源的又一重要辅助指标.     

B细胞特异性激活蛋白/CD30双标记在经典型Hodgkin淋巴瘤中的表达及意义

关于经典型Hodgkin淋巴瘤（CHL）的细胞属性,目前普遍的观点支持起源于B细胞。在实际工作中我们常规诊断的主要依据之一还是免疫组织化学方法,但由于CHL的特殊的形态学表现（反应性细胞较多,背景杂乱）常常影响对免疫分型的判断。我们探讨免疫组织化学双标记法就是为了寻求一种在实际工作中简单实用,而又能把肿瘤性H／RS细胞显示出来,对其细胞属性进行准确判断的研究方法。     

免疫组织化学标记在鉴别结节性淋巴细胞为主型与富于淋巴细胞的经典型霍奇金淋巴瘤中的作用

霍奇金淋巴瘤（HL）分为结节性淋巴细胞为主型（NLPHL）和经典型（CHL）,因两者具有不同的免疫表型与临床特点必须加以区别。其中,NLPHL与富于淋巴细胞的经典型HL（LRCHL）的鉴别较困难。B细胞特异性激活蛋白（BSAP）和BOB.1（B-cell oct-binding protein 1）是目前研究较多的两种B细胞特异性转录因子,已有学者指出在NLPHL中的L＆H细胞表达这两种蛋白。目前国内对EB病毒在这两种病变中的表达情况研究较少,     

眼结膜黏膜相关淋巴组织边缘带B细胞淋巴瘤临床病理分析

目的 探讨眼结膜黏膜相关淋巴组织边缘带B细胞淋巴瘤(marginal zone B cell lymphoma of mucosa-associated lymphoid tissue)(简称为MALT淋巴瘤)的临床病理特征、治疗及预后.方法 对15例眼结膜MALT淋巴瘤患者的临床病理资料进行回顾性分析及随访,复查和完善HE及免疫组化染色切片,4例进行Ig基因重排克隆性分析.结果 (1)15例患者中,男性5例,女性10例,中位年龄42岁,病史平均20个月.(2)病理形态:黏膜下大量密集淋巴样细胞弥漫浸润,并有模糊淋巴滤泡样结节.浸润细胞多为小～中等大小的淋巴样细胞及单核样B细胞.(3)免疫表型:浸润细胞CD20、CD79a、BCL-2均(+),CD3、CD5、CD10、Cyclin D1、TdT均(-).(4)Ig基因克隆性分析:4例均呈单克隆.(5)随访:随访时间2～35个月,截止随访日期,所有患者均生存,且病变无复发.结论 眼结膜MALT淋巴瘤好发于中年女性,结膜红肿突起为主要特征,镜下以小细胞样边缘带B细胞为主,具有典型MALT淋巴瘤的免疫表型和惰性临床经过,预后良好.     

弥漫大B细胞淋巴瘤基因表达谱的研究进展

弥漫大B细胞淋巴瘤（DLBCL）是最常见的一类淋巴瘤,占非霍奇金淋巴瘤的30％左右。DLBCL的临床表现、形态学、免疫表型及遗传学特征极具异质性,越来越多的证据表明其可能并不是一个真正独立的病种。最新的WHO淋巴造血组织肿瘤分类列出了DLBCL的一些形态学亚型,但这种形态学分型不仅与预后的关系尚存在争议,而且诊断的可重复性差,所以实际应用价值不大。大多数DLBCL患者经过化学治疗后可以获得缓解,但半数患者仍在短期内复发并死亡。国际预后指数（international prognostic index,IPI）是通过年龄、功能状态、血清乳酸脱氢酶水平、累及结外部位的数量以及肿瘤临床分期等5个临床特征对患者进行评分,具有相当的预后判断价值。     

眼部原发性黏膜相关淋巴组织结外边缘区B细胞淋巴瘤的临床病理分析

近年来眼部淋巴瘤日益多见,其中眼附属器淋巴瘤占老年人眼眶原发性恶性肿瘤的首位。根据2001年WHO恶性淋巴瘤分类诊断标准,眼附属器淋巴瘤大多属于黏膜相关淋巴组织结外边缘区B细胞淋巴瘤（MALT淋巴瘤）,其临床和组织病明学表现、治疗及预后均有其特殊性。我们对眼部MALT淋巴瘤的临床和病理资料进行了回顾性分析。     

Oct2蛋白在淋巴瘤中的表达及意义

目的通过检测淋巴瘤中Oct2蛋白的表达,观察其特异性和敏感性,探讨Oct2在淋巴瘤诊断和分类中的意义. 方法应用免疫组织化学EnVision法检测并观察129例不同类型淋巴瘤和10例淋巴结反应性增生(RLH)中的Oct2蛋白表达.结果 RLH中Oct2主要表达在生发中心细胞,而B细胞淋巴瘤则为弥漫阳性表达.Oct2阳性率在B细胞淋巴瘤为97.7%(85/87),与CD20阳性率90.8%(79/87)相比差异无统计学意义(P>0.05);与CD79α阳性率84.7%(61/72)相比差异有统计学意义(P<0.05).Oct2阳性率在T细胞淋巴瘤为3.8%(1/26);在结节性淋巴细胞为主型霍奇金淋巴瘤(NLPHL)和经典型霍奇金淋巴瘤(CHL)分别为3例均阳性和46.2%(6/13),后两组间比较P>0.05.结论作为B细胞淋巴瘤一种新的相对特异而敏感的标记物,Oct2抗体可能有助于淋巴瘤的诊断和分类,可作为诊断B细胞淋巴瘤的首选标记物之一.     

经典型霍奇金淋巴瘤中CXCR5的表达及临床病理意义

目的 探讨经典型霍奇金淋巴瘤(classic Hodgkin lymphoma, CHL)中CXCR5的表达及意义。方法 采用免疫组化EnVision两步法检测33例CHL中CXCR5的表达,分析CXCR5在CHL四种亚型中的表达情况及临床病理诊断意义;同时收集10例ALK阳性间变性大细胞淋巴瘤(anaplastic large cell lymphoma, ALCL)和10例ALK阴性ALCL作为对照组,对比分析CXCR5的表达情况。结果 33例CHL中,31例CXCR5阳性(93.94%):其中结节硬化型15例(15/16,93.75%)、混合细胞型12例(12/13,92.31%)、淋巴细胞丰富型2例,淋巴细胞消减型2例。CHL中CXCR5的表达情况分别为：33例CD30阳性和PAX5弱阳性中31例阳性(93.94%);14例CD15阴性中12例阳性(85.71%);26例CD20阴性中24例阳性(92.31%);6例LMP1阴性中5例阳性;11例EBER阴性中10例阳性(90.91%)。对照组20例ALCL中,肿瘤细胞CXCR5均阴性。结论 CHL中CXCR5阳性率较高,当肿瘤...     

弥漫性大B细胞淋巴瘤中hENT1的表达及意义

目的 探讨hENT1在生发中心B细胞(germinal center B cell-like,GCB)型与非GCB(non-GCB)型弥漫性大B细胞淋巴瘤(diffuse large B-cell lymphoma,DLBCL)中的表达及意义.方法 采用免疫组化PV 6000两步法检测CD10、BCL-6、MUM1蛋白在DLBCL的表达并对DLBCL进行亚型分类,同时检测hENT1蛋白的表达,探讨免疫组化染色结果和临床病理参数及预后的关系.结果 (1)hENT1蛋白在DLBCL的GCB及non-GCB亚型中表达差异有显著性(P=0.031,P<0.05).(2)hENT1的表达与患者性别、年龄、部位、LDH高低、Ann Arbor分期、有无B症状的差异均无统计学意义.(3)对76例DLBCL患者进行生存分析,中位随访时间21个月.Log-rank检验GCB/non-GCB组累计生存率差异有统计学意义(P=0.010).结论 DLBCL中non-GCB型患者比例较大,预后差.在治疗过程中,检测hENT1的表达为能否使用核苷类药物提供依据.     

Signal transmission through the B cell-specific MB-1 molecule at the pre-B cell stage.

Specific binding of antigens to the surface immunoglobulin M (sIgM) triggers B cells with several biochemical events involved in receptor-mediated signal transmission for proliferation and differentiation into antibody-producing cells. Recent studies with the Digitonin lysis method identified the sIgM-associated component, IgM-alpha (B34)/Ig-beta, as the possible candidate for the transducer molecule(s) in the immunoglobulin receptor-mediated signal transmission. The 34 kd protein (B34 or IgM-alpha) of this component is suggested to be encoded by the B cell-specific mb-1 gene. We prepared monoclonal antibodies which recognize the mb-1 gene product (MB-1) and studied the functional role of MB-1 in the signal transmission in B lineage cells. Using murine pre-B lymphoma cells (18-81 and 70Z/3), we demonstrated the early phase increase of the intracellular [Ca2+]i concentration and the subsequent inhibition of the proliferation by the monoclonal anti-MB-1 antibody (11-18-5). These results clearly demonstrate signal transmission through the surface MB-1 molecule on B lineage lymphomas. This MB-1-mediated signal transmission in pre-B cell lines would suggest an alternative function of MB-1 acting at the pre-B cell stage.     

淋巴瘤凋亡调节基因bcl—x mRNA及蛋白的表达

目的 探讨凋亡调节基因ｂｃｌ－ｘ在淋巴瘤细胞凋亡调控和肿瘤发生中的作用及在淋巴瘤诊断中的价值。方法 收集３０例新鲜标本和１０９例存蜡块（均包括淋巴反应性增生和Ｔ、Ｂ常见类型淋巴瘤）,用逆转录－聚合酶链反应（ＲＴ－ＰＣＲ）和免疫组化枸橼酸－微波－ＡＢＣ法分别观察ｂｃｌ－ｘ ｍＲＮＡ和其蛋白的表达及分布。结果 ＲＴ－ＰＣＲ显示３０例新鲜标本中均有ｂｃｌ－ｘ的转录,其中２９例可见ｂｃｌ－ｘ条带,１３例出     

Inactivation of p16 INK4a /CDKN2A gene may be a diagnostic feature of large B cell lymphoma leg type among cutaneous B cell lymphomas

The World Health Organization-European Organization for Research and Treatment of Cancer has individualized three main categories among the primary cutaneous B cell lymphoma (PCBCL): leg-type primary cutaneous large B cell lymphoma (PCLBCL leg type), primary cutaneous follicle center lymphoma (PCFCL), and primary cutaneous marginal zone lymphoma (PCMZL). The genetic features of 21 PCBCL cases (six PCLBCL leg type four PCFCL large cells, seven PCFCL small cells, and four PCMZL) were investigated by comparative genomic hybridization (CGH array). Fluorescent in situ hybridization (FISH) analysis was performed to confirm CGH array data and to detect lymphoma-associated gene rearrangements. p14 ( ARF )/p16 ( INK4a ) CDKN2A gene quantification, methylation analysis, and immunohistochemical detection were also performed. CGH array showed a higher number of recurrent genetic imbalances in PCLBCL leg type (mean 62) than in PCFCL large cells (mean 34). PCFCL small cells and PCMZL exhibited fewer chromosomal alterations (mean 24 and 9). FISH analysis provided concordant results with CGH array data in 97% (98 of 101) assays and demonstrated a t(8;14)(q24;q32) in two of six PCLBCL leg type. Recurrent deletions in 9p21 (p14 ( ARF )/p16 ( INK4a ) CDKN2A) were a constant finding in PCLBCL leg type (six of six). Conversely, PCFCL large cells exhibited recurrent 1p36 deletions (four of four) without deletion in 9p21 (zero of four). The diagnostic and prognostic impact of the p16 ( INK4a ) CDKN2A gene status in PCBCL should therefore be confirmed on a larger series.     

Improved efficacy of soluble human receptor activator of nuclear factor kappa B (RANK) fusion protein by site-directed mutagenesis

Abstract

Soluble human receptor activator of nuclear factor kappa B fusion immunoglobulin (hRANK-Ig) has been considered as one of the therapeutic agents to treat osteoporosis or diseases associated with bone destruction by blocking the interaction between RANK and the receptor activator of nuclear factor kappa B ligand (RANKL). However, no scientific record showing critical amino acid residues within the structural interface between the human RANKL and RANK complex is yet available. In this study, we produced several mutants of hRANK-Ig by replacement of amino acid residue(s) and tested whether the mutants had increased binding affinity to human RANKL. Based on the results from flow cytometry and surface plasmon resonance analyses, the replacement of E¹²⁵ with D¹²⁵, or E¹²⁵ and C¹²⁷ with D¹²⁵ and F¹²⁷ within loop 3 of cysteine-rich domain 3 of hRANK-Ig increases binding affinity to human RANKL over the wild-type hRANK-Ig. This result may provide the first example of improvement in the efficacy of hRANK-Ig by protein engineering and may give additional information to understand a more defined structural interface between hRANK and RANKL.     

PAX8 and PAX5 are differentially expressed in B‐cell and T‐cell lymphomas

Aims: The purpose of this study was to evaluate the expression patterns of B‐cell specific activator protein (BSAP)/PAX5 and PAX8 in a wide variety of B‐cell and T‐cell neoplasms. Methods and results: A wide range of B‐cell and T‐cell neoplasms were subjected to immunohistochemical staining with antibodies against BSAP/PAX5 and PAX8 (polyclonal, pPAX8; monoclonal, mPAX8). Ten non‐neoplastic lymph node specimens were examined with the same panel. All of the tested neoplastic and non‐neoplastic B‐cells reacted with the BSAP/PAX5 and pPAX8 antibodies, but did not show reactivity with the mPAX8 antibody. All tested T‐cell neoplasms were negative using the BSAP/PAX5, pPAX8 and mPAX8 antibodies. Conclusions: This is the first study to show the absence of reactivity to an mPAX8 antibody in an expanded panel of B‐cell lymphomas as well as in a variety of T‐cell neoplasms. In contrast to the mPAX8 antibody, the pPAX8 antibody shows nuclear positivity in non‐neoplastic B cells and mature B‐cell neoplasms; however, this expression is probably a result of cross‐reactivity with PAX5. Given that many laboratories use the pPAX8 antibody, a clear understanding of the differential staining patterns is necessary. The differential diagnosis of a B‐cell lymphoma should be entertained when a pPAX8‐positive, epithelial marker‐negative neoplasm of uncertain primary origin is encountered.     

儿童非何杰金淋巴瘤的DNA含量和免疫表型的研究

应用流式细胞术和免疫组化技术，对６３例儿童非何杰金淋巴瘤的ＤＮＡ含量、免疫表型和核仁组织区相关蛋白进行了研究，结果表明：异倍体率、Ａｇ－ＮＯＲ值及增殖指数（ＰＩ）随着组织学分级增高而增大，且ＰＩ可作为判断预后的一项定量指标；Ａｇ－ＮＯＲ与ＰＩ呈正相关；异倍体与二倍体肿瘤累积生存率无显著差异；累积生存率未定型淋巴瘤＞Ｔ细胞淋巴瘤＞Ｂ细胞淋巴瘤。     

Expression of p63 in reactive hyperplasias and malignant lymphomas

p63 is a recently described p53 homologue. It is involved in survival and differentiation of reserve/stem cells in epithelia. To obtain new insights into the role of p63 in malignant lymphomas (MLs), immunohistochemical staining for p63 and p53 was performed in 126 cases of MLs. p63 was expressed in 38 cases of MLs (30.2%) including 32/61 cases (52.5%) of diffuse large B-cell lymphoma (DLBCL), 1/8 cases (12.5%) of precursor T-lymphoblastic lymphoma (T-LBL), 4/14 cases (28.6%) of follicular lymphoma, 1/6 cases (16.7%) of T/NK cell lymphoma. Among p63 positive cases, p63 was strongly expressed in 15/32 cases of DLBCL and 1/1 case of T-LBL. p63 was not expressed in mantle cell lymphomas, peripheral T-cell lymphomas, marginal zone B-cell lymphomas, plasma cell myelomas and Hodgkin's lymphomas. p63 was coexpressed with p53 in 18/38 p63 positive cases in which only 4 cases were strongly coexpressed. All p63+/p53+ cases were DLBCL. p63 overexpression (above 30%) cases showed significant poor survival (p=0.0228) in DLBCL. However, there was no statistically significant correlation between p63 expression and IPI score on Multivariate analysis. We could speculate that p63 could act indirectly as an oncogene by inhibiting p53 functions. Stage of differentiation of neoplastic lymphocytes appears to have a correlation with p63 expression in MLs.     

骨代谢中甲状旁腺激素对相关蛋白和核因子κB受体活化因子的调节

背景：甲状旁腺激素是影响骨代谢功能轴最主要的因素。同时也是调控骨保护素和核因子κB受体活化因子配基表达的重要激素。 目的：通过查阅甲状旁腺激素对骨保护素、核因子κB受体活化因子配基调控作用的相关文章,并对其进行综述。 方法：以“甲状旁腺激素,骨保护蛋白,核因子κB受体活化因子”或“Parathyroid hormone, osteoprotegerin, receptor activator of nuclear factor κB ligand”为检索词,由第一作者通过计算机检索 CNKI、HighWire数据库中关于“甲状旁腺激素与骨保护素/核因子κB受体活化因子配基/核因子κB受体活化剂”的相关的论文报告。选择的文章内容与甲状旁腺激素对信号通路的影响有关、近期发表的文献,按纳入和排除标准对文献进行筛选,共纳入31篇文章。 结果与结论：甲状旁腺激素是调节骨代谢最主要的因素,通过增强破骨细胞活动增强而实现的。核因子κB受体活化因子配基是调节骨吸收的关键因子,它通过与核因子κB受体活化剂结合发挥功能。核因子κB受体活化因子配基与核因子κB受体活化剂结合后,启动核因子κB受体活化因子配基信号转导,骨保护素则与核因子κB受体活化因子配基竞争性结合核因子κB受体活化剂,核因子κB受体活化因子配基/骨保护素比值决定破骨细胞分化、成熟及功能。长时间、大强度的运动条件下,机体内甲状旁腺激素的变化是否对于骨保护素、核因子κB受体活化因子配基有影响,进而调节骨代谢的吸收与合成？还有待进一步的研究。     

Expression of serine 194-phosphorylated Fas-associated death domain protein correlates with proliferation in B-cell non-Hodgkin lymphomas

Fas-associated death domain protein is a key component of the extrinsic apoptotic pathway. In addition, in animal models, Fas-associated death domain protein phosphorylation at serine 194 has been shown to affect cell proliferation, especially in T lymphocytes. The importance of Fas-associated death domain protein phosphorylation at serine 194 for the proliferation of B lymphocytes, however, is uncertain. Here we show in reactive lymph nodes that serine 194 phosphorylated Fas-associated death domain protein is expressed predominantly in the dark (proliferative) zone of germinal centers. In B-cell non-Hodgkin lymphoma cell lines, serine 194 phosphorylated Fas-associated death domain protein levels are substantially higher in highly proliferating cells and lower in serum-starved cells. We also used immunohistochemical analysis to assess Fas-associated death domain protein phosphorylation at serine 194 expression in 122 B-cell non-Hodgkin-type lymphomas. The mean percentage of serine 194 phosphorylated Fas-associated death domain protein positive tumor cells was 81% in Burkitt lymphoma, 41% in diffuse large B-cell lymphoma, 18% in follicular lymphoma, 18% in plasma cell myeloma, 12% in extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, 11% in mantle cell lymphoma, and 2% in chronic lymphocytic leukemia/small lymphocytic lymphoma (P < .0001, Kruskal-Wallis test). Furthermore, in chronic lymphocytic leukemia/small lymphocytic lymphoma, serine 194 phosphorylated Fas-associated death domain protein was detected predominantly in proliferation centers. In the entire study group, the percentage of cells positive for serine 194 phosphorylated Fas-associated death domain protein correlated significantly with the proliferation index Ki-67 (Spearman R = 0.9, P < .0001). These data provide evidence that serine 194 phosphorylated Fas-associated death domain protein is involved in the proliferation of normal and neoplastic B cells and has features of a novel proliferation marker.