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     

PTTG与C—MYC在非霍奇金淋巴瘤中的表达及意义

目的：探讨原癌基因PTTG与C-MYC在非霍奇金淋巴瘤（NHL）中的表达及临床病理意义。方法：应用免疫组织化学S—P法检测PTrG和C—MYC在NHL与对照组织中的表达，分析它们的表达与NHL的组织类型、恶性程度，临床分期及PTTG与C—MYC两者问的相关性。结果：与对照组织相比，NHL中PTTG显著高表达（P〈0．05），且T细胞淋巴瘤比B细胞淋巴瘤表达率高（P〈0．01），两组淋巴瘤中侵袭性强亚型中表达率均高于其对应的惰性亚型组（P均〈0．05）；临床分期晚期组表达率高于早期组（P〈0．05）。NHL中C—MYC表达率仅6．1％，且与PTrG之间无相关性（rs=-0．368，P〉0．05）。结论：PTTG高表达但不通过活化C—MYC来参与NHL的发生、发展。     

MMP-2及TIMP-2表达在良恶性葡萄胎鉴别诊断中的价值探讨

目的：寻求一种能早期诊断恶性葡萄的新方法,方法：采用免疫组化法观察良恶性葡萄胎组织中MMP－2及TIMP－2的表达情况。结果：MMP－2在恶性葡萄胎和良性葡萄胎的阳性率分别为73．3％和20．05（P＜0．01）;TIMP－2为33．3％和26．7％（P＞0．05）。结论：MMP－2检测可作为鉴别良恶性葡萄胎的重要参考指标。     

B淋巴瘤6号染色体微卫星不稳定性及杂合性缺失

目的：探讨6号染色体微卫星不稳定性（microsatellite instability，MSI）及杂合性缺失（loss of heterozygosity，LOH），碱基错配修复系统GTBP和hMLH1基因蛋白在B细胞淋巴瘤（B cell non-hodgkin’s lymphoma，B-NHL）发生学上的意义。方法：选取6号染色体上7对多态微卫星标记，结合PCR及银染技术，采用凝胶成像图象分析系统，分别检测58例B-NHL染色体微卫星MSI及LOH。对其中23例BNHL细胞进行EnVinsion法检测MMR的功能基因GTBP、hMLH1的表达情况。结果：弥漫性大B细胞淋巴瘤（diffuse large B-celllymphoma，DLBCL）与滤泡性淋巴瘤（follicular lymphoma，FL）中GTBP和hMLH1蛋白表达差异无统计学意义，P值分别为0．98和1．30。原发生于淋巴结内与淋巴结外的GTBP、hMLH1蛋白表达差异无统计学意义，P值分别为0．54和0．67。GTBP蛋白在高、低度恶性表达之间差异无统计学意义，P=1．00；而hMLH1蛋白表达在低度恶性较高度恶性高，P=0．99。在位点D6S275 MSI的发生率为7．5％（4／53），其中包括DLBCL2例，FL和BCLL／SLL各1例，LOH总的发生率达66．0％（35／53），其中包括DLBCL19例（19／21，90．5％），FL8例（8／13，61．5％），B-CLL／SLL8例（8／19，42．1％），DLBCL的LOH率同B-CLL／SLL和FL相比，差异有统计学意义，P=10．60。结论：hMLH1和GTBP错配修复基因蛋白表达与BNHL组织学类型、肿瘤的发生部位可能无关系。位点D6S275可能存在一个抑癌基因，该基因的缺失以及与错配修复基因hMLH1突变的关系对B细胞淋巴瘤的发生作用有待进一步研究。     

恶性淋巴瘤nm23、CD44的表达及恶性度与疗效的关系

目的 探讨nm23,CD44在不同恶性程度淋巴瘤中的表达规律及其与临床疗效的关系。方法 应用免疫组化Envision法检测恶性淋巴瘤患者病变组织nm23-H1,CD44-V6蛋白的表达,根据染色阳性数据数采用四级半定量法评估阳性反应强度并分为低表达和高表达两组。淋巴瘤的病理分类和恶性度分级按REAL标准。结果 （1）在正常淋巴组织中nm23,CD44呈低水平表达。（2）nm23在霍奇金病（HD）中表达低于非霍奇金淋巴瘤（NHL）,差异有显著性（P＜0．05）;而CD44在两者间表达无显著性差异（P＞0．05）;在NHL中随REAL恶性度的提高,nm23和CD44表达均增强,差异有显著性（P＜0．001）。（3）nm23低表达组CR率74．5％,高表达组45．5％;CD44低表达组CR率67．2％,高表达组46．4％,差异均有显著性（P＜0．05）。结论 nm23,CD44在正常淋巴组织和恶性淋巴瘤中具有不同的表达规律,其表达的强度可反映淋巴瘤的恶性程度;并且能预测患者的疗效。     

非霍奇金林巴瘤中细胞凋亡与细胞增殖的研究

目的 了解非霍奇金淋巴瘤（NHL）中细胞凋亡与细胞增殖间的关系，探讨两者在NHL发生与发展中的作用。方法 利用TdT介导的dUTP缺口末端标记（TUNEL）法和PCNA免疫组化技术原位检测60例NHL中的细胞凋亡和增殖水平，计算凋亡指数（AI）和增殖指数（PI）。结果 B细胞性NHL中，随着恶性度增高，AI和PI均增高（P＜0．05），T细胞性NHL中高度恶性组PI明显高于低度恶性组（P＜0．05），而AI在两组之间无显著性差异（P＞0．05）。AI和PI呈显著正相关（r=0．704，P＜0．01）。结论 在NHL中细胞凋亡与增殖之间可能存在密切的联系，共同参与了NHL的发生和恶性进展。对细胞凋亡和增殖水平的检测可能有助于NHL恶性度及预后的判断。     

COX-2在B细胞非霍奇金淋巴瘤中的表达及临床意义

目的探讨环氧合酶．2（COX-2）在B细胞非霍奇金淋巴瘤（B-NHL）中的表达及临床意义。方法采用免疫组化S-P法检测43例B—NHL和10例良性淋巴结病变组织中COX-2的表达。结果COX-2在B．NHL中的阳性表达率为55．8％（24／43）,明显高于对照组,差异具有统计学意义（P〈0．05）。COX-2的表达与B—NHL的临床分期和病理组织学等级具有相关性：Ⅲ-Ⅳ期B-NHL患者COX-2蛋白的表达高于Ⅰ／Ⅱ期患者（P〈0．05）,侵袭性B—NHL患者COX-2蛋白的表达高于惰性组（P〈0．01）。COX-2阴性表达患者的5年生存率高于COX-2阳性表达患者（P〈0．05）。COX模型显示COX-2是一个独立的不良预后指标。结论COX-2在B-NHL的发生和发展中具有重要作用,并且是一个有用的预后指标。     

脑星形细胞瘤 Fas和 FasL的表达及细胞凋亡与肿瘤恶性程度相互关系的初步探讨

目的：对脑星形细胞瘤Fas和FasL的表达水平及细胞凋亡与肿瘤恶性程度之间的关系进行初步探讨。方法：对41例脑星形细胞瘤标本采用免疫组化法（S－P法）检测Fas和FasL的表达率及表达强度,采用TUNEL法检测凋亡指数。结果：本组星形细胞瘤Fas和FasL的表达率分别为65．9％和78．0％;Fas和FasL的表达率与其病理分级有关（X^2分别为17．552和10．749,P均＜0．05）;Fas和FasL的表达强度也与其病理分级呈负相关（r分别为－0．660和－0．506,P均＜0．01）。本组星形细胞瘤的凋亡指数为0．51－1．57,凋亡指数与肿瘤病理分级有关（F＝18．828,P＜0．05）。结论：本组大部分星形细胞瘤均有Fas和FasL的表达,表达率和表达强度均随肿瘤恶性程度增高而明显下降,星形细胞瘤的凋亡指数随肿瘤恶性程度增高而明显增高。     

垂体肿瘤转化基因PTTG在NHL中的表达及其意义

目的：探讨垂体肿瘤转化基因PTTG（pituitary tumor transforming gene）在非霍奇金淋巴瘤（NHL）中的表达，并研究其表达与NHL临床病理指标的关系。方法：采用原位杂交法和免疫组化法检测50例NHL患者肿瘤组织和20例良性淋巴结炎组织中PTTG mRNA及其蛋白的表达。结果：PTTG mRNA在NHL和对照组的阳性表达率分别为54．0％（27／50）和20．0％（4／20），PTTG蛋白在NHL和对照组的阳性表达率分别为50．0％（25／50）和15．0％（3／20），NHL中PTTG mRNA及其蛋白的阳性表达率及表达分级比较均高于对照组。PTTG mRNA的表达与NHL的恶性程度和临床分期呈正相关（r=0．366，P=0．009；r=0．438，P=0．001）。NHL中PTTG mRNA表达与其蛋白表达成等级正相关（r=0．831，P〈0．01）。NHL中PTTG mRNA表达与近期疗效呈负相关（r=-0．354，P〈0．05）。结论：NHL中PTTG高表达。PTTG表达水平与NHL生物学行为可能有关。     

儿童非霍奇金淋巴瘤MDM2和p53蛋白表达的研究

 目的 探讨儿童非霍奇金淋巴瘤（NHL）患者癌基因MDM2和抑癌基因p53的表达与NHL的恶性程度和预后的关系。方法 46例儿童NHL患者作为病例组,12例儿童淋巴结炎患者作为对照组。用免疫组织化学超敏S-P染色法,检测病例组NHL患者、对照组淋巴结炎患者病理组织的MDM2蛋白和p53蛋白的表达情况,阳性细胞为胞核染成黄色~棕黄色,阳性细胞数≥10 %为MDM2免疫组织化学阳性（MDM2蛋白过度表达）;阳性细胞数>5 %为p53免疫组织化学阳性。结果 病例组MDM2蛋白过度表达率为65.2 %,与对照组比较差异有统计学意义（P＜0.01）。p53蛋白阳性率为19.6 %,与对照组比较差异无统计学意义（P＞0.05）。MDM2蛋白过度表达率在病理分类高度恶性、患者血清LDH增高之间差异均有统计学意义（P＜0.05）,与患者的B状态间差异有统计学意义（P＜0.01）。p53蛋白阳性率与病理工作分类、临床分期、B状态、血清LDH之间差异均无统计学意义（P＞0.05）。MDM2蛋白过度表达与p53蛋白阳性之间没有关联性。结论 儿童NHL患者MDM2基因的过度表达率较高;MDM2过度表达与儿童NHL患者的不良状况、不良预后有关;儿童NHL患者p53阳性率较低。     

Quantitative analysis detects ubiquitous expression of apoptotic regulators in B cell non-Hodgkin's lymphomas.

To determine whether the expression levels of Bcl-2 family apoptotic regulators are correlated with the histopathological heterogeneity of B cell non-Hodgkin's lymphomas (NHL), we quantified their expression in malignant B cell populations isolated from 33 biopsy samples, including small lymphocytic lymphoma (SLL, n = 9), mantle cell lymphoma (MCL, n = 8), follicular lymphoma (FL, n = 8), and diffuse large cell lymphoma (DLCL, n = 8). Normal B cells purified from reactive lymph nodes and tonsil (n = 3) were used as controls. Cell lysates were analyzed by Western blotting, and signals quantified by densitometry. Expression of Bcl-2 and its homologues, Bcl-xL, Bcl-xS, Bax, Bad, Bak and Bag-1, was detected in all NHL cases, with wide variations between histological subtypes and within each subtype. Statistically significant differences were: (1) a higher level of Bad expression in DLCL compared to FL and MCL; (2) a lower level of Bak expression in FL compared to DLCL, SLL and MCL; and (3) a higher Bag-1 expression level in FL compared to SLL. When compared to NHL cells, normal B cells showed a higher level of Bax expression, and a lower level of Bcl-xL expression. Thus, quantitative analysis shows ubiquitous expression of Bcl-2 family proteins in normal and neoplastic B cells; the variations in expression levels may contribute to both the B-NHL clinicopathological diversity and the different apoptotic sensitivities of normal B cells vs B-NHL cells.     

惰性B 细胞非霍奇金淋巴瘤与肝炎病毒感染相关性分析

目的:分析惰性B 细胞非霍奇金淋巴瘤（B cell non-Hodgkin lymphoma,B-NHL）不同亚型患者乙型肝炎病毒（hepatitis B virus,HBV ）及丙型肝炎病毒（hepatitis C virus,HCV ）感染的情况,探讨惰性B-NHL不同亚型与肝炎病毒感染的相关性。方法:回顾性分析中国医学科学院血液病医院1994年1 月至2014年1 月收治的733 例初诊惰性B-NHL患者的肝炎病毒感染资料。与全国一般人群相对照,比较惰性B-NHL患者与全国一般人群肝炎病毒感染的差异。比较分析惰性B-NHL各亚型患者肝炎病毒感染的情况,并探讨其相关性。结果:733 例惰性B-NHL患者乙肝表面抗原（hepatitis B surface antigen ,HBs-Ag）阳性率为7.9% ,与全国一般人群比较,差异无统计学意义（7.9% vs . 7.2% ,P = 0.548）。 在惰性B-NHL中,脾边缘区淋巴瘤（splenic marginal zone lymphoma,SMZL）48例,HBs-Ag阳性率为18.8% ,明显高于全国一般人群（18.8% vs . 7.2% ,P = 0.002）、其他惰性B-NHL（18.8% vs . 7.2% ,P = 0.004）及其他边缘区淋巴瘤（marginal zone lymphoma ,MZL）患者（18.8% vs . 7.1%,P = 0.005）。惰性 B-NHL其他亚型患者 HBs-Ag阳性率比较全国一般人群,差异均无统计学意义（P > 0.05）。 在HBs-Ag阳性患者中,乙肝“大三阳”在惰性B-NHL不同亚型中无显著性差异,但乙肝“小三阳”在SMZL 组占16.7% ,明显高于其他惰性B-NHL组（16.7% vs . 4.7% ,P < 0.001）。 惰性B-NHL患者抗丙型肝炎病毒抗体（hepatitis C virus antibody,HCV-Ab）阳性率为1.9% ,较全国一般人群明显升高（1.9% vs . 0.4% ,P < 0.001）。 其中慢性淋巴细胞白血病（chronic lymphocytic leukemia ,CLL）、淋巴浆细胞性淋巴瘤/ 华氏巨球蛋白血症（lymphoplasmacytic lymphoma/waldenstr?m macroglobulinemia ,LPL/WM）、SMZL、毛细胞白血病（hairy cell leukemia ,HCL ）、结内边缘区淋巴瘤（nodal marginal zone B-cell lymphoma,NMZL）组患者抗HCV-Ab 阳性率分别为2.2% 、2.5% 、4.2% 、3.0% 、3.7% 均较全国一般人群明显升高（均P <0.05）。 而慢性B 淋巴细胞增殖性疾病不能分类（B-cell lymphoproliferative disorders,unclassified ,B-LPD-U）、黏膜相关淋巴组织结外边缘区淋巴瘤（extranodal marginal zone B-cell lymphoma of mucosa-associated tissue lymphoma ,MALT）、B-幼淋巴细胞白血病（B-cell prolymphocytic leukaemia,B-PLL ）、滤泡性淋巴瘤（follicular lymphoma ,FL）组与全国一般人群比较,差异均无统计学意义（均P > 0.05）。 结论:SMZL 患者HBs-Ag阳性率明显高于全国一般人群及其他惰性B-NHL各亚型,提示HBV 感染与我国SMZL 的发生发展存在一定的相关性。      

Sensitivity to Fas-mediated apoptosis is null or weak in B-cell non-Hodgkin's lymphomas and is moderately increased by CD40 ligation.

The Fas receptor (APO-1/CD95) is capable of inducing apoptosis of lymphoid cells and is expressed in some non-Hodgkin''s lymphomas (NHLs). Fas expression is up-regulated at the surface of normal B cells upon triggering of the CD40 receptor. In this report, we investigated the sensitivity of NHLs to Fas-mediated apoptosis induced by anti-Fas monoclonal antibodies (MAbs) and its possible modulation by CD40 ligation in 18 NHL biopsy samples of various histological subtypes. Flow cytometric analysis showed that the fraction of Fas-expressing lymphoma cells was highly variable from sample to sample (from 1% to 93%, mean value 46%). The frequency of apoptotic cells was not significantly increased upon treatment with an anti-Fas MAb compared with control MAb in the 18 NHL cases analysed. The sensitivity of lymphoma cells to Fas-mediated apoptosis was correlated neither with the histological subtypes nor with the level of Fas expression. Activation of neoplastic B cells by CD40 ligation resulted in significant increases in Fas expression and Fas-induced apoptosis among the five B-NHL cases tested. The overall increase in apoptotic rates was moderate and remained lower in tumour samples than in control CD40-activated normal tonsil B cells. Altogether, our results indicate that the sensitivity to Fas-induced apoptosis is null or weak in NHL cells, irrespective of their histological subtype, and that it can be increased to a moderate and variable degree by CD40 ligation on neoplastic B cells. This may be an impediment to the development of Fas-based therapies for NHLs.     

Mouse rosettes and surface immunoglobulin in small lymphocytic lymphoma. Importance in immunophenotyping and differential diagnosis.

Cell suspensions from lymphoid tissue of 82 small lymphocytic lymphoma (SLL), 8 intermediate lymphocytic lymphoma (ILL), 286 other B-non-Hodgkin's lymphoma (B-NHL), and 248 reactive lymphadenopathy (RLA) cases were analyzed to evaluate the diagnostic significance of mouse-rosette (M-rosette) assay, and surface immunoglobulin clonality (SIg) and level of expression. In SLL, 55 were M-rosette positive (67.07%) and 72 SIg positive (87.8%), with weak fluorescence in 63 and strong fluorescence in 9 cases. Of 10 SIg-negative cases, 9 were M-rosette positive; of 27 M-rosette-negative cases, 26 were SIg positive. Seven of the nine cases with strong fluorescence were M-rosette positive. In other B-NHL, 252 were M-rosette negative (88.11%) and 245 SIg positive (85.66%), with strong fluorescence in 211 and weak fluorescence in 34 cases. Thirty-two of the 34 cases with weak fluorescence were M-rosette negative. Of the RLA cases, 213 were M-rosette negative (85.89%) and 1 SIg positive (0.4%). The study demonstrated the independent expression of M-rosettes and SIg in SLL and their complementary role in diagnosis. It showed that positive results for M-rosettes and weak fluorescence are characteristic of SLL, that M-rosette negativity and strong fluorescence are characteristic of other B-NHL, and that M-rosette negativity and polyclonal SIg are characteristic of RLA. In 26 cases with paired data for CD5, M-rosettes, and SIg, a positive result for M-rosettes was superior to CD5 in differentiating SLL from other B-NHL. Intermediate lymphocytic lymphoma frequently showed weak SIg fluorescence and M-rosette negativity.     

新疆维吾尔自治区乌鲁木齐地区466例非霍奇金淋巴瘤临床病理特征分析

 目的　探讨新疆维吾尔自治区乌鲁木齐地区不同民族非霍奇金淋巴瘤（NHL）的临床病理特点。方法　收集466例NHL标本,复查HE和免疫组织化学染色结果,重新诊断、分型。结果　466例中B细胞性NHL 369例（79.2 %）,T细胞性NHL 97例（20.8 %）;结内193例（41.4 %）,结外273例（58.6 %）;最常见组织学类型为弥漫大B细胞淋巴瘤、小淋巴细胞淋巴瘤／慢性淋巴细胞白血病、黏膜相关淋巴组织结外边缘区B细胞淋巴瘤、NK／T细胞淋巴瘤、外周T细胞淋巴瘤、滤泡性淋巴瘤。维吾尔族T淋巴母细胞淋巴瘤（T-LBL）和间变性大细胞淋巴瘤（ALCL）比例分别为7.5 %（9／120）和4.2 %（5／120）,高于汉族的1.3 %（4／308）和2.3 %（7／308）（χ2＝11.276,P＝0.001;χ2＝1.137,P＝0.286）。而汉族结外NK／T细胞淋巴瘤比例为7.1 %（22／308）,高于维吾尔族的3.3 %（4／120）,差异无统计学意义（χ2＝2.196,P＝0.138）。其余各亚型在不同民族间差异皆无统计学意义（均P＞0.05）。结论　乌鲁木齐地区NHL结外发病高于结内,B细胞性淋巴瘤的发病明显高于我国内地。维吾尔族和汉族B-NHL发病构成在整体上差别不大,但是在T细胞NHL中,维吾尔族T-LBL和ALCL高于汉族,而汉族结外NK／T细胞淋巴瘤高于维吾尔族,这些差异是否与新疆维吾尔自治区的民族与地域差异有关,还需要进一步的研究证实。     

Long-term follow-up of indolent lymphoma patients treated with high-dose sequential chemotherapy and autografting: evidence that durable molecular and clinical remission frequently can be attained only in follicular subtypes.

PURPOSE: To evaluate the prognostic relevance of molecular monitoring of minimal residual disease in indolent lymphomas receiving high-dose sequential chemotherapy and autografting. PATIENTS, MATERIALS, AND METHODS: A polymerase chain reaction- (PCR-)based strategy was used to evaluate the presence of residual tumor cells in a panel of 70 indolent lymphoma patients: 40 with follicular (FCL), 14 with small lymphocytic (SLL), and 16 with mantle-cell (MCL) lymphomas. They were treated either with first-line (n = 61) or second-line (n = 9) therapy with an intensified high-dose chemotherapy program followed by peripheral-blood progenitor cells autografting. The Bcl-1, Bcl-2, and immunoglobulin gene rearrangements were used as lymphoma-specific markers. Overall, a molecular marker was obtained from the diagnostic tissue in 60 of 70 patients (86%). Results The collection of PCR-negative cells and the achievement of posttransplantation molecular remission (MR) were common in patients with FCL subtype (54% and 70%, respectively), whereas they were not frequent among SLL and MCL (25% and 12.5%, respectively) patients. With a median molecular follow-up of 75 months, an 88% incidence of relapse was observed among patients never attaining MR. In contrast, relapse incidence was only 8% among patients attaining a durable MR (P <.005). At present, 26 patients (20 with FCL and six with non-FCL) are long-term survivors in absence of clinical and molecular disease. CONCLUSION: Our results indicate that among indolent lymphomas, FCL and non-FCL subtypes show a significantly different behavior in terms of MR achievement, and MR after intensive chemotherapy and autografting is predictive for a prolonged disease-free survival, whereas persistent PCR positivity is associated with a high risk of relapse.     

Small cell variant of mantle cell lymphoma is an indolent lymphoma characterized by bone marrow involvement, splenomegaly, and a low Ki-67 index

Mantle cell lymphoma (MCL) is recognized as a well-defined B cell neoplasm characterized by overexpression of cyclin D1 (CCND1), with "classical" and "aggressive" variant subtypes. A small-cell variant of MCL (small-MCL), resembling small lymphocytic lymphoma/chronic lymphocytic lymphoma (CLL/SLL), has been added to the World Health Organization classification. However, to the best of our knowledge, there have been no studies focusing on this neoplasm. In the present study, we analyzed 15 cases of CCND1-positive small-MCL, including immunohistochemical analysis of Ki-67 and CCND1 expression, and compared our findings with those of 151 cases of classical MCL. Morphologically, most small-MCL showed a diffuse growth pattern (76.9%), whereas others featured a very thin mantle zone pattern resembling a reactive follicle (23.1%). Bone marrow involvement and splenomegaly occurred significantly more frequently in small-MCL than in classical MCL (P < 0.05). Ki-67 expression in small-MCL was lower than in classical MCL (mean [± 2 SD] 12.5 ± 17.3% and 25.2 ± 25.5%, respectively; P < 0.001), but there was no significant difference in CCND1 expression (P = 0.2445). The 5-year survival rate in small-MCL was 83.3%. Although there was no significant difference in outcome between small-MCL and classical MCL (P = 0.287), only one small-MCL patient died of the disease. Thus, small-MCL constitutes a specific subset of indolent lymphoma with distinguishing features, possibly making a major contribution to the accuracy of therapeutic decisions. In addition, clinicians should be aware of the possible presence of small-MCL to avoid making a misdiagnosis of follicular hyperplasia or CLL/SLL.     

IDO 在弥漫大 B 细胞淋巴瘤中的表达及其临床意义

目的：探讨弥漫大 B 细胞淋巴瘤组织中吲哚胺2,3双加氧酶（indoleamine 2,3- dioxygenase,IDO）的表达及意义。方法：收集2007年1月至2012年12月四川省肿瘤医院存档蜡块63例,其中弥漫大 B 细胞淋巴瘤组织41例,炎症反应性增生组22例,采用免疫组织化学技术检测 IDO 的表达,并分析与临床病理资料的关系及其临床意义。结果：弥漫大 B 细胞淋巴瘤组织中 IDO 阳性率为56.1%,明显高于反应性增生炎症组织22.7%,差异有统计学意义,P =0.011;IDO 表达水平与 Hans 分型、B 症状具有相关性,P =0.000、0.035;IDO的表达与患者的年龄、性别、分期、结外受侵数目、IPI、ECOG、LDH 无明显相关,P ﹥0.05;IDO 与弥漫大 B 细胞淋巴瘤的近期疗效具有相关性,P =0.001;Log - rank 单因素生存分析显示 IDO 的表达水平、Hans 分型、B 症状及 IPI 评分差异有统计学意义,P =0.009、0.003、0.000、0.030;Cox 多因素生存分析,仅 IDO 表达水平具有显著性差异,P =0.024。结论：IDO 的高表达,可能参与弥漫大 B 细胞淋巴瘤的免疫逃逸相关。IDO 高表达与弥漫大 B 细胞淋巴瘤疾病进展、疗效及预后不良相关,提示 IDO 可能成为弥漫大 B 细胞淋巴瘤患者的独立预后因子及新的治疗靶点。