原发性睾丸弥漫性大B细胞淋巴瘤的临床病理及预后

目的观察原发性睾丸弥漫性大B细胞淋巴瘤的临床病理、免疫表型特征及患者存活情况,探讨该肿瘤的病理诊断、鉴别诊断及预后。方法按WHO（2001）淋巴瘤分类标准收集14例原发性睾丸弥漫性大B细胞淋巴瘤,中位年龄62岁,按AnnArbor分期标准,Ⅰ期10例,Ⅱ期3例,Ⅳ期1例。11例有随访资料,其中3例存活,最长存活时间86个月;8例死亡,存活时间5～19个月,中位存活时间为11个月。总结14例的组织病理学、免疫表型特征,并进行存活分析。结果单侧睾丸无痛性肿大是最常见的临床表现。形态学变型全部为中心母细胞性。免疫分型,生发中心样B细胞型（GCB型）1例,非生发中心样B细胞型（non—GCB型）13例。10例p53蛋白表达阳性,肿瘤细胞增殖活性高,6例肿瘤细胞表达bcl-2蛋白。存活分析表明,1、2、5年生存率分别为45．5％、17．0％、17．0％。结论原发性睾丸弥漫性大B细胞淋巴瘤多为外周活化的B细胞起源,预后差,易复发和转移;病理活检加免疫表型检测对肿瘤的诊断和鉴别诊断有重要作用。     

弥漫大B细胞淋巴瘤免疫表型分型与预后的关系

目的 探讨弥漫大B细胞淋巴瘤（DLBCL）的免疫表型之生发中心B细胞样（GCB）和非GCB两个亚型的特征及其与DLBCL预后的关系。方法 根据肿瘤细胞免疫组织化学EnVision法标记CD10、bc1-6、MUM-1的表达情况,将133例DLBCL分为GCB和非GCB两个亚型。对以下指标的5年总生存率（OS）及5年无进展生存率（PFS）进行了比较：（1）CD10、bc1-6和MUM-1的阳性和阴性病例;（2）GCB亚型与非GCB亚型;（3）不同国际预后指数（IPI）分组中GCB亚型与非GCB亚型的关系。结果 133例DLBCL中,44例（33．1％）CD10阳性,48例（34．6％）bc1-6阳性,60例（45．1％）MUM-1阳性。CD10阳性DLBCL患者的5年OS及PFS均明显高于CD10阴性患者（P=0．041和0．031）;bc1-6阳性DLBCL患者的PFS明显高于bc1-6阴性患者（P=0．044）,MUM．1阳性DLBCL患者的5年0s及PFS均明显低于MUM-1阴性患者（P=0．031和0．028）。GCB型54例（40．6％）,非GCB型79例（59．4％）。GCB型5年OS及PFS均明显高于非GCB型（P=0．004和0．003）。国际预后指数（IPI）0-1分组及2-5分组中,GCB型5年OS及PFS均明显高于非GCB型（IP10-1分组P=0．019和0．014,2-5分组P=0．006和0．009）,其中IPI2-5分组中的非GCB预后最差。结论 DLBCL亚型及其与IPI联合分析可以作为预测患者预后的有效指标。     

弥漫性大B细胞淋巴瘤基因表达谱的初步研究

目的探讨弥漫性大B细胞淋巴瘤（DLBCL）不同免疫表型组的基因表达谱状况。方法根据CD10、bcl-6和MUM1的表达状况对156例DLBCL进行分组：CD10^＋和（或）bcl-6^＋、MUM1-（第1组）;CD10^＋和（或）bcl-6^＋、MUM1^＋（第2组）;CD10^-和bcl-6^-、MUM1^＋（第3组）。从各组中各选择3例共（9例）临床分期为Ⅳ期的病例标本,另取3例正常扁桃体组织作为对照,采用Affymetrix U133 plus2．0寡核苷酸芯片研究12例样本的基因表达谱。结果通过unsupervised等级聚类分析,12例样本被分成了4组,分别命名为A、B、C、D组。经与免疫表型分组结果对照显示两种分组结果完全一致：A、B、C组分别对应第1、2、3组,D组对应正常对照组。在DLBCL病例组中（A、B、C组）有81个基因显著表达下调,有86个基因显著表达上调。而其中的一个组（B组）虽然具有混合性生发中心B细胞样（GCB,A组）和活化的外周血B细胞样（ABC,C组）DLBCL的免疫表型,但在聚类分析中发现其基因表达谱与A组和C组均不同,有45个基因表达上调,并且有27个特异性表达基因。结论初步结果显示,DLBCL全基因组表达谱在分子水平上有不同的亚群,且可能通过免疫表型来区分。还提示基因表达谱B组DLBCL可能存在除细胞起源以外的不同异质性因素,而这种因素可能与DLBCL的发病机制相关。     

弥漫性大B细胞淋巴瘤500例构成比及免疫表型分析

目的 按照WHO(2008版)造血与淋巴组织肿瘤分类,分析弥漫性大B细胞淋巴瘤(DLBCL)各亚型的构成比情况、免疫表型特点,及其总体生存率.方法 按照新分类,结合形态学观察,利用免疫组织化学、基因重排、原位杂交、荧光原位杂交(FISH)等技术对500例DLBCL,进行回顾性分析和归类,收集随访资料,并对生发中心B细胞(GCB)型和非GCB型组之间、老年人EB病毒(EBV)阳性的DCBCL亚型和非特殊型弥漫性大B细胞淋巴瘤(DLBCL-NOS)之间进行总体生存率比较.结果 500例中DLBCL-NOS约占77.2%(386/500),其次是老年人EBV阳性的DLBCL占9.4%(47/500),然后依次是原发中枢神经系统的DLBCL(4.4%,22/500)、原发纵隔(胸腺)的大B细胞淋巴瘤(2.8%,14/500)、富于T细胞/组织细胞的大B细胞淋巴瘤(2.6%,13/500),其余类型均属于比较罕见的.DLBCL-NOS按照形态学分类以中心母细胞性最为常见,约占95.1%(367/386);按免疫组织化学分型,非GCB型组在DLBCL-NOS中约占68.5%(219/320),GCB型组占28.4%(91/320),而CD5阳性DLBCL仅占3.1%(10/320).总体生存率比较,GCB型组和非GCB型组总体生存率差异无统计学意义(P=0.93),老年人EBV阳性的DLBCL组总体生存率与年龄匹配前、后的DLBCL-NOS组差异均无统计学意义(P值分别为0.13和0.28).对形态学表现为灰区的淋巴瘤病例进行FISH检测,发现了1例"双打击"(double-hit)淋巴瘤.结论 DLBCL-NOS在DLBCL中占绝大多数,其次是老年人EBV阳性的DLBCL和原发中枢神经系统的DLBCL,其他类型均属少见或罕见类型.按照Hans分类进行免疫组织化学分型,非GCB型占多数,GCB型和非GCB型分组总体生存率没有显著性差异.老年人EBV阳性的DLBCL组和用年龄匹配前后的DLBCL-NOS组的总体生存率均无显著性差异.

Abstract：

Objective To study the immunophenotype and overall survival of diffuse large B-cell lymphoma (DLBCL) classified according to the 2008 World Health Organization classification of tumors of hematopoietic and lymphoid tissues. Methods Five hundred cases of DLBCL were retrospectively analyzed with histologic review, immunohistochemistry, gene rearrangement study, in situ hybridization and fluorescence in situ hybridization. Follow-up data were collected. The overall survival rates of germinal center B-cell (GCB) and non-germinal center B-cell (non-GCB) subtypes, as well as those of DLBCL, not otherwise specified (NOS) and Epstein-Barr virus (EBV)-positive DLBCL of the elderly, were compared.Results DLBCL-NOS was the commonest subtype which accounted for 77.2% (386/500) of the cases.EBV-positive DLBCL of the elderly, primary DLBCL of central nervous system, primary mediastinal (thymic) large B-cell lymphoma and T cell/histiocyte-rich large B-cell lymphoma accounted for 9. 4%(47/500), 4. 4% (22/500), 2. 8% (14/500) and 2. 6% (13/500), respectively. 68. 5% (219/320) of DLBCL-NOS belonged to non-GCB subtype. The percentage of GCB subtype and CD5-positive subtype were 28.4% (91/320) and 3. 1% (10/320), respectively. Comparison of the overall survival, GCB and non-GCB immunophenotypic groups have no significant difference (P = 0. 93). And the same result in which of the EBV-positive DLBCL of the elderly and DLBCL-NOS group, before and after age matched (P =0. 13 and O. 28, respectively). A double-hit lymphoma was found by FISH detection, which presenting as gray zone lymphoma in morphology. Conclusions By using Hans algorithm, GCB and non-GCB subtypes show no significant difference in overall survival. EBV-positive DLBCL of the elderly and DLBCL-NOS also do not have significant difference in overall survival. Fluorescence in situ hybridization technique is helpful in identification of DLBCL with rare phenotypes.     

原发胃肠道弥漫性大B细胞淋巴瘤的免疫分型及其与预后的关系

目的 了解原发胃肠道弥漫性大B细胞淋巴瘤的免疫分型,并比较Choi、Tally和Hans 分型及其与预后的关系.方法 复习90例原发胃肠道弥漫性大B细胞淋巴瘤患者的临床及病理资料并进行随访,应用Kaplan-Meier法、Log-rank检验和Cox比例风险回归模型对临床资料、实验室检测结果 进行生存分析及单因素和多因素预后分析.免疫表型检测采用EnVision和EliVision法,选用的抗体有CD20、CD3ε、CDl0、bcl-6、MUM-1、CD5、bcl-2、GCET1、FOXP1、LMO2、BLIMP1和Ki-67等.结果 (1)年龄为27～83岁,中位年龄58岁,男女比为1.31:1;胃肿瘤58例,占64.4%(58/90);肠肿瘤32例,占35.6%(32/90).(2)肿瘤细胞均表达CD20抗原,均不表达CD3ε和CD5;CD10、bcl-6、MUM-1(30%/80%阈值)的表达率分别为17.8%(16/90)、75.6%(68/90)、52.2%(47/90)/43.3%(39/90),GCET1、FOXP1、LMO2的表达率分别为50.0%(45/90)、45.6%(41/90)、23.3%(21/90),bcl-2、BLIMP1的表达率分别为42.2%(38/90)、8.9%(8/90),Ki-67阳性指数20%～95%,中位数为80%.Hans分型:51.1%为生发中心B细胞型(GCB型),48.9%为非GCB型;Choi分型:55.6%为GCB型,44.4%为活化B细胞(ABC)型;Tally分型:34.4%为GCB型,65.6%为非GCB型.(3)67.8%(61/90)的患者接受化疗,68.9%(62/90)的患者接受手术.患者的2、3和5年总体生存率分别为58.5%、52.8%和49.8%,CHOP方案(环磷酰胺+多柔比星+长春新碱+泼尼松)治疗组的2、3和5年总体生存率分别为68.5%、61.2%和52.9%.结论 Hans和Choi分型各亚型比例差别不大,Tally分型中非GCB型较GCB型比例增高.三种分型的各亚型均存在GCB型优于非GCB/ABC型的趋势.Log-rank检验单因素分析提示乳酸脱氢酶(LDH)水平、国际预后指数(IPI)、化疗、手术、B症状、病变数量、临床分期对预后有影响.Cox比例风险回归模型多因素分析提示Hans分型、Choi分型、化疗、手术、LDH和Lugano分期是独立的预后因素.

Abstract：

Objective To study the immunophenotype and prognostic significance of primary gastrointestinal diffuse large B-cell Iymphoma, with reference to Hans, Choi and Tally algorithms. Methods The clinicopathologic features and follow-up data in 90 cases of primary gastrointestinal diffuse large B-cell lymphoma were analyzed by Kaplan-Meier method, Log-rank test and Cox regression model.Immunohistochemistry was carried out using EliVision and EnVision methods for CD20, CD3ε, CD10,bcl-6, MUM-1, CDS, bcl-2, GCET1, FOXP1, LMO2,BLIMP1 and Ki-67. Results The age of patients studied, 64. 4% (58/90) involved the stomach and 35.6% (32/90) involved the intestine. The immunohistochemical findings were as follows: 100% positivity for CD20, 0% for CD3ε and CD5, 17.8% (16/90) for CD10, 75.6% (68/90) for bcl-6, 52. 2% (47/90) for MUM-1 (cut off was 30%), 43.3%(39/90) for MUM-1 (cut off was 80%), 50.0% (45/90) for GCET1, 45.6% (41/90) for FOXP1,23.3%(21/90) for LMO2, 42.2% (38/90) for bcl-2 and 8.9% (8/90) for BLIMP1. The Ki-67 index ranged from 20% to95% (median =80%). According to Hans algorithm, 51.1% of the cases belonged to germinal center B-cell (GCB) subtype and 48.9% belonged to non-GCB subtype. In contrast, Choi algorithm classified 55.6% cases as GCB subtype and 44. 4% as activated B-cell (ABC) subtype.According to Tally algorithm, 34. 4% were of GCB subtype and 65.6% of non-GCB subtype. Most of the patients (67. 8% ,61/90) received chemotherapy and 68.9% (62/90) underwent surgical resection. The overall 2, 3 and 5-year survival rates were 58. 5%, 52. 8% and 49. 8%, respectively. The overall 2, 3 and 5-year survival rates in the CHOP therapy group were 68.5%, 61.2% and 52. 9%, respectively.Conclusions There is no significant difference in ratio between the GCB and non-GCB/ABC subtypes by Hans and Choi algorithms. The non-GCB subtype seems to be more prevalent according to Tally algorithm.Although there is no significant difference in survival between GCB and non-GCB/ABC subtypes by the 3algorithms, GCB subtype tends to show a better survival. In univariate analysis, LDH level, international prognostic index, chemotherapy, surgical resection, B symptoms, number of involved sites and clinical stage are found to have prognostic significance. In multivariate analysis, Choi algorithm, Tally algorithm,chemotherapy, surgical resection, LDH level and clinical stage are independent prognostic factors.     

上海地区弥漫性大B细胞淋巴瘤的生发中心B细胞样型显著偏低

目的 探讨中国上海地区弥漫性大B细胞淋巴瘤(DLBCL)的生发中心B细胞(GCB)样型与非GCB样型的分布以及可能影响因素.方法 应用免疫组织化学EnVision法分析124例来自该院的原发DLBCL中CD10、bcl-6、MUMl、GCET1和FOXP15种蛋白的表达,采用Hans和Choi两种免疫表型分型法进行分型.其中118例应用荧光原位杂交技术检测t(14;18)和bcl-6基因重排情况.结果 使用Hans法对124例DLBCL进行分型,27例(22%)为GCB样型,97例(78%)为非GCB样型.使用Choi法进行分型显示34例(27%)为GCB样型,90例(73%)为非GCB样型(即ABe样型).GCB样型显著低于非GCB样型(P=0.0001).t(14;18)易位仅4例(3%),3例发生于GCB样型中.bcl-6基因重排阳性的病例为46例(39%),高发于GCB样型中.bcl-6基因重排与bcl-6蛋白表达没有明显相关性.结论 中国上海地区DLBCL的GCB样型显著低于非GCB样型,可能与其DLBCL的t(14;18)低水平发生有关.     

结内外弥漫性大B细胞淋巴瘤的免疫表型和分化特征及预后的比较

目的探讨弥漫性大B细胞淋巴瘤（DLBCL）的临床生物学特征和预后并比较结内与结外的差异。方法分析142例DLBCL的临床病理资料,结内90例,结外52例（胃肠30例,其他22例）,并随访2～108个月,制备组织芯片,并经免疫组织化学EnVision法染色,观察CD10、bcl-6、MUM1蛋白的表达并进一步区分其生发中心B细胞（GCB细胞）和非生发中心B细胞的分化特征。结果胃肠道DLBCL常为Ⅰ～Ⅱ期,国际预后指标评分低,预后也好于结内及其他结外DLBCL。单个抗原的表达率,CD10为19％（27例）,bcl-6为51％（72例）,MUM1为58％（82例）。36％（51例）的DLBCL显示GCB细胞分化特征,64％（91例）的DLBCL显示非GCB细胞分化特征。结外DLBCL的bcl-6的表达（63％）高于结内DLBCL（43％）。在不同的结外部位,甲状腺等部位多见为GCB细胞分化的DLBCL;睾丸等部位多见为非GCB细胞分化的DLBCL。结论DLBCL显示生发中心B细胞和非生发中心B细胞分化特征,结内外以及结外不同部位的DLBCL有着不同的生物学特征和预后。     

BCL-6、MYC和p53基因异常与弥漫性大B细胞淋巴瘤免疫学亚型及预后的关系

目的 探讨弥漫性大B细胞淋巴瘤(diffuse large B-cell lymphoma,DLBCL)患者BCL-6、MYC和p53基因的异常情况,用并分析它们与免疫学亚型及预后的关系.方法 应用间期荧光原位杂交技术分析46例DLBCL患者BCL-6、MYC和p53基因的异常情况,用免疫组织化学技术(Envision法)对DLBCL进行CD3、CD10、CD20、BCL-6、MUM-1、BCL-2和Ki-67标记,根据Hans的分类方法将其分为生发中心B细胞型(germinal center B cell,GCB型)和非生发中心B细胞型(non-germinal center B cell,non-GCB型).结果 46例患者中,BCL-6基因重排10例,BCL-6重排与BCL-6蛋白的表达两者之间差异无统计学意义(P=0.245).BCL-6基因重排与DLBCL患者的总生存时间(P=0.138)和无进展生存时间(P=0.095)无统计学相关性.MYC重排4例,全部见于GCB型.p53基因缺失14例,p53基因缺失组与p53基因正常组相比,生存时间差异有统计学意义(总生存时间:P=0.046;无进展生存时间::P=0.043).结论 间期荧光原位杂交技术可以快速、准确、灵敏的检测BCL-6、MYC和p53基因的异常.BCL-6基因重排与BCL-6蛋白的表达之间无统计学相关性.MYC重排多见于GCB亚型组,p53基因缺失的患者预后较差.p53基因可以作为判断DLBCL预后的参考指标.     

bcl-6基因5'非编码区突变与弥漫性大B细胞淋巴瘤生发中心亚型的相关性

目的 分析弥漫性大B细胞淋巴瘤(DLBCL)中bcl-6基因5'非编码区突变频率及与其生发中心B细胞(GCB)型的相关性.方法 对60例DLBCL行套式PCR检测t(14;l8)易位,并经免疫组织化学EnVision两步法进行GCB和非GCB分子分型.PCR扩增bcl-6主要突变区,测序检测突变位点.结果 60例中7例(11.7%)发生t(14;18)易位,为主要断裂点发生转位;联合免疫组织化学分析和t(14;18)易位检测,筛选出GCB型18例和非GCB型42例;5'非编码区总突变率为20.0%(12/60),GCB型突变率为7/18,非GCB型突变率为11.9%(5/42);+363和+469位点频繁发生突变.结论 DLBCL的bcl-65'非编码区发生突变频率较国外低,突变多发生于GCB型中.t(14;18)易位检测有助于DLBCL的分子分型.     

睾丸弥漫性大B细胞淋巴瘤58例临床病理及免疫表型

目的 观察睾丸弥漫性大B细胞淋巴瘤(DLBCL)的临床病理及免疫表型特点,探讨其病理诊断及预后.方法 对58例睾丸DLBCL进行回顾性临床病理研究,包括形态学复习、免疫组织化学(EnVision法)染色、EB病毒编码小RNA(EBER) 1/2原位杂交以及预后相关因素分析.结果 58例睾丸DLBCL患者平均年龄62.1岁,中位年龄65岁.多数病程较短,51例(87.9％)就诊时处于临床Ⅰ～Ⅱ期;48例(82.8％)为单侧睾丸受累.12例(20.7％)伴同侧腹股沟淋巴结肿大,少有其他器官累及.52例(89.7％)病理形态学表现为中心母细胞样细胞在睾丸间质内弥漫性浸润,并浸润曲细精管.睾丸白膜受侵、血管浸润分别见于14例(24.1％)和10例(17.2％).Hans分型以非生发中心B细胞型为主(48/58,82.8％).缺乏EB病毒感染.所有病例行病变睾丸切除,35例(60.3％)接受了术后化疗和(或)放疗.随访率为82.8％ (48/58),其中28例(58.3％)患者死亡;1、3、5年总体生存率分别为55.7％、31.6％和27.6％.年龄＞60岁、B症状、血清乳酸脱氢酶水平升高、高临床分期及未接受术后联合治疗者预后差.结论 睾丸DLBCL确诊时以局部病变为主,低临床分期,有一定的病理形态学特征,多为非生发中心型DLBCL,预后不良;术后联合化疗可延长患者的生存期.     

弥漫大B细胞淋巴瘤中Prdx6的表达及其预后意义

目的 探讨过氧化物酶6(peroxiredoxin-6,Prdx6)在弥漫大B细胞淋巴瘤(diffuse large B-cell lymphoma,DLBCL)中的表达及其预后意义.方法 回顾性分析286例DLBCL中Prdx6的表达及与临床病理特征和预后之间的关系.结果 Prdx6在DLBCL中的表达高于正常淋巴结...     

Bcl-6 and Bcl-2 protein expression in diffuse large B-cell lymphoma and follicular lymphoma: correlation with 3q27 and 18q21 chromosomal abnormalities.

The bcl-2 gene on chromosome 18 at q21 and the bcl-6 gene on chromosome 3 at q27 are both highly regulated during B-cell differentiation and show an inverse relationship of expression in the normal secondary lymphoid follicle. The objective of this study was to investigate the relationship between bcl-2 and bcl-6 protein expression and the relationship between protein expression and the corresponding chromosomal alterations in malignant lymphomas, including those associated with the germinal center. Expression of bcl-2 and bcl-6 proteins was studied in 55 cases of diffuse large B-cell lymphoma (DLBCL) and 21 cases of follicular lymphoma (FL), and the results correlated with the presence of t(14;18) and 3q27 abnormalities in a subset of 52 cases with cytogenetic analysis. These cases were selected to represent a spectrum of nodal and extranodal lymphomas, including those with and without a t(14;18). It was shown that the neoplastic cells in 71% of DLBCLs and 100% of FLs expressed bcl-6 protein. Expression of bcl-6 was seen more frequently in diffuse large B-cell lymphomas with large noncleaved morphology compared with immunoblastic morphology (82% v 27%, P = .0015), but failed to correlate with 3q27 abnormalities. Thirty-eight percent of cases with 3q27 abnormalities were bcl-6 protein negative, whereas 85% of cases without a 3q27 abnormalities were bcl-6 protein positive. Expression of bcl-2 protein was shown in 51% DLBCLs (nodal v extranodal, 71% v 30%, P = .012). bcl-2 protein was expressed in 89% of FLs with t(14;18), in contrast to 25% of FLs without t(14;18) (P = .016). In DLBCL and FL with t(14;18), the most common pattern of expression was bcl-2+/bcl-6+. In lymphomas without t(14;18), there was not an inverse relationship between bcl-2 and bcl-6 protein expression. In conclusion, these data suggest that mechanisms other than gene rearrangements can deregulate bcl-2 and bcl-6 expression in lymphomas, and there does not appear to be an inverse relationship between these two proteins as seen in the normal germinal center.     

Intrachromosomal rearrangement of chromosome 3q27: an under recognized mechanism of BCL6 translocation in B-cell non-Hodgkin lymphoma

Balanced reciprocal translocations involving chromosomal region 3q27, which led to identification of the BCL6 protooncogene, are one of the most common recurrent chromosomal abnormalities reported in B-cell non-Hodgkin lymphomas (B-NHL). Cloning of the breakpoints of these translocations has facilitated the identification of a number of BCL6 partners including immunoglobulin genes and more than 20 non-immunoglobulin genes on almost all human chromosomes. Fusion of BCL6 with these genes leads to deregulated BCL6 expression because of substitution of its promoter with that of the translocation partner. Despite the promiscuous nature of BCL6 translocations, intrachromosomal rearrangements of the BCL6 gene have not been well recognized. In the present study, we present evidence for intrachromosomal rearrangements, because of interstitial deletions and inversions, involving region 3q27 as an overlooked mechanism of BCL6 deregulation. These rearrangements accounted for 3/20 (15%) of all BCL6 translocations occurring in B-NHL, including follicular lymphomas, diffuse large B-cell lymphomas, and marginal zone B-cell lymphomas, diagnosed at our institute. In addition to confirming previously described partner loci on chromosome 3, we also identified a novel BCL6 partner locus (3p24) that to our knowledge has not been reported previously. Our data should help facilitate the identification of new BCL6 partner genes, which may enhance our understanding of the clinical and biological role of BCL6 in B-NHL pathogenesis.     

弥漫大B细胞淋巴瘤中CD27的表达及临床意义

目的探讨弥漫大B细胞淋巴瘤(diffuse large B cell lymphoma, DLBCL)中CD27的表达及其临床意义。方法采用免疫组化EnVision法检测143例DLBCL组织中CD27蛋白的表达;应用FISH技术检测DLBCL组织中MYC、BCL-2、BCL-6基因重排情况。结果 143例DLBCL中,CD27蛋白阳性者46例,阳性率为32.2%。CD27阳性组中BCL-2重排阳性率(17.4%)明显高于CD27阴性组(4.1%),差异有统计学意义(P<0.01)。CD27阳性组病死率(30.4%)明显高于CD27阴性组(15.5%),差异有统计学意义(χ²=4.326,P=0.038)。CD27阳性者与阴性者的Kaplan-Meier生存曲线差异有显著性(χ²=4.485,P=0.034),阳性组生存期较短。结论 CD27高表达与DLBCL预后密切相关,可作为临床预后评价的指标之一。     

弥漫大B细胞淋巴瘤中miR-5585-3p的表达及其意义

目的探讨miR-5585-3p在弥漫大B细胞淋巴瘤(diffuse large B-cell lymphoma,DLBCL)中的表达与临床病理特征的相关性及其预后意义。方法选取12例DLBCL石蜡标本进行基因芯片扫描,依据fold change≥1.5、P≤0.05筛选出差异性表达的miRNAs,miR-5585-3p是其中之一。采用qRT-PCR检测95例DLBCL石蜡标本中miR-5585-3p的表达,15例淋巴结反应性增生组织作为对照,并结合患者临床病理学资料进行分析。结果 miR-5585-3p在DLBCL中的表达量显著高于淋巴结反应性增生组织(P0.001),且non-GCB亚型miR-5585-3p的表达水平是GCB型的2.4倍(P=0.006)。miR-5585-3p高表达与淋巴瘤国际预后指数(IPI)呈正相关(P=0.005)。Kaplan-Meier生存分析显示:DLBCL中高表达miR-5585-3p的患者生存率明显低于miR-5585-3p低表达者(P=0.049)。预后多因素Cox分析显示,年龄60岁(P=0.010)、IPI评分3~5分(P=0.004)、高表达miR-5585-3p(P=0.014)为DLBCL独立不良预后指标。结论 miR-5585-3p高表达可能与DLBCL不良预后有关。     

Interstitial deletion of 8(q13q22) in diffuse large B-cell gastric lymphoma

A presentation of intracranial tumor in bilateral and unilateral retinoblastoma with or without family history is termed as trilateral retinoblastoma (TRB). It always occurs either as a pineal tumor or supra/parasellar tumor, which differ in presentation and prognosis. We report here the first case of TRB with transmission of retinoblastoma gene (RB1) deletion from an unaffected mother (a carrier), presenting as concurrent intracranial neoplasm with bilateral retinoblastoma. The presence of RB1 mutation in both child and mother could be responsible for development of intracranial neoplasm which occurred simultaneously with bilateral RB in our patient. Our patient, who had a suprasellar mass, received radiation and intrathecal chemotherapy, and died 6 months after diagnosis. The occurrence of intracranial tumor in an asymptomatic stage can be avoided by routine computed tomography (CT) and magnetic resonance imaging (MRI) scan, and improved survival can be achieved by aggressive multimodality therapy.     

A novel t(3;8)(q27;q24.1) simultaneously involving both the BCL6 and MYC genes in a diffuse large B-cell lymphoma

Diffuse large B-cell lymphomas (DLBCLs) are a clinically and biologically heterogeneous group of hematologic malignancies. Specific genetic aberrations underlie some of this heterogeneity. These genetic events include distinct and separate translocations resulting in the dysregulated expression of either BCL6 protein with the t(3;14)(q27;q32) or c-MYC protein with the t(8;14)(q24;q32), as a consequence of the juxtaposition of these oncogenes with heterologous promoters or enhancers, such as those of the immunoglobulin heavy chain gene. Here, we report the case of a patient with DLBCL with a unique t(3;8)(q27;q24.1) that involves the BCL6 and MYC genes. We know of no previous report of this translocation in DLBCL, which simultaneously affects two key genes implicated in lymphomagenesis and may reflect a novel genetic mechanism in neoplastic transformation.