弥漫大B细胞淋巴瘤中miR-339-5 p的表达及意义

目的：检测miR-339-5p在弥漫大B细胞淋巴瘤(diffuse large B-cell lymphoma, DLBCL)中的表达,探讨miR-339-5p表达与DLBCL临床病理特征的关系。方法采用显色原位杂交技术检测123例 DLBCL 和20例淋巴结反应性增生( reactive lymphoid hyperplasia, RH)组织中miR-339-5p的表达,并采用免疫组化EnVision两步法检测DLBCL组织中Ki-67和BCL-6蛋白的表达,分析miR-339-5p与BCL-6表达的相关性及二者表达与DLBCL临床病理特征的关系。结果 DLBCL组织中miR-339-5p的阳性率(39．8%,49/123)显著低于RH组织(90．0%,18/20)。活化的B细胞型(ABC型)DLBCL组织中miR-339-5p阳性率(31．0%,22/71)明显低于生发中心的次级B细胞型(GCB型)(51．9%,27/52)。 miR-339-5p在DLBCL中表达降低与Ann Arbor分期晚以及国际预后指数IPI评分高有关(P均<0．05)。 ABC型、GCB型DLBCL中miR-339-5p阴性患者生存率均明显低于miR-339-5p阳性患者(P均<0．01)。 DLBCL中miR-339-5p与BCL-6蛋白表达呈显著负相关(P<0．01)。结论miR-339-5p低表达可能与DLBCL进展和预后不良相关。     

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。     

STAT3在艾滋病相关弥漫性大B细胞淋巴瘤中的表达及意义

目的：探讨STAT3在艾滋病相关弥漫性大B细胞淋巴瘤(ADIS/HIV-related diffuse large B-cell lymphoma,HIV-DLBCL)中的表达及意义。方法：收集21例HIV-DLBCL组织标本作为实验组。对照组15例标本,分别为6例HIV阴性的DLBCL(non-HIV-DLBCL)、4例HIV阳性淋巴结反应性增生(HIV-reactive hyperplasia,HIV-RH)、5例HIV阴性淋巴结反应性增生(non-HIV-RH)。采用免疫组化检测各样本中STAT3的表达情况,并结合患者的临床病理因素分析。结果：HIV-DLBCL中STAT3总阳性表达率为76.19%,以胞核表达为主占81.25%;non-HIV-DLBCL中STAT3总阳性表达率为66.67%,以胞核表达为主占50%;两组总阳性率及核阳性率差异无统计学意义(P>0.05)。HIV-RH和non-HIV-RH中,STAT3仅表达于淋巴滤泡细胞;HIV-DLBCL中STAT3表达率与良性病变组具有显著性差异(P<0.05)。STAT3在non-GCB型HIV-DLBCL中的表达明显高于GCB型HIV-DLBCL(P<0.01),与性别、年龄、发病部位及临床分期等因素无关(P>0.05)。结论：STAT3在HIV-DLBCL和non-HIV-DLBCL中均呈高表达,且以核表达为主,提示STAT3过表达与DLBCL的发生有关;STAT3表达与HIV-DLBCL的免疫表型有关,因不同免疫表型DLBCL的预后存在差异,提示STAT3可能是HIV-DLBCL的潜在预后标志物。     

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...     

Comparative clinicopathological study of primary CNS diffuse large B-cell lymphoma and intravascular large B-cell lymphoma

Primary CNS diffuse large B-cell lymphoma (CNS DLBCL) is confined to the CNS, and constitutes a distinct entity. In the present study a series of 40 Japanese patients with CNS DLBCL who presented with neurological, but not systemic symptoms, was reviewed. Median survival was 18.7 months. CD5, CD10, Bcl-6, MUM-1, and Bcl-2 were positive in 30%, 10%, 84%, 100%, and 93% of patients, respectively. All CD10-negative patients had non-germinal center B-cell type. There was no significant difference in survival among the immunophenotypic subgroups. CNS DLBCL appeared to be homogenous as a group, which prompted the comparison with another distinct extranodal entity, intravascular large B-cell lymphoma (IVLBCL) in Japanese patients. CNS DLBCL patients did not differ in age, sex, or immunophenotype, including CD5 positivity, from IVLBCL patients, but were significantly less likely to have poor prognostic parameters than IVLBCL patients: the international prognostic index score was low or low–intermediate in 86% of CNS DLBCL patients and high or high–intermediate in 98% of IVLBCL patients. Notably, despite this difference, their survival curves almost overlapped. The present study highlights the issue of clinical distinctiveness of aggressive extranodal lymphomas, the peculiar migration and localization of which should be further clarified.     

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。     

p52 Activation in monomorphic B-cell posttransplant lymphoproliferative disorder/diffuse large B-cell lymphoma without BAFF-R expression

Posttransplantation lymphoproliferative disorders (PTLD) are associated with Epstein-Barr virus (EBV) and activate the NF-κB pathway. B-cell activating factor (BAFF) modulates cell growth and survival in non-Hodgkin's lymphomas. However, there are few studies of EBV, BAFF/BAFF-R signaling, and NF-κB1 and NF-κB2 pathway activation in PTLD. Diffuse large B-cell lymphomas (DLBCL) in two different clinical contexts, immunocompetent patients (DLBCL/IC; n = 30) or posttransplantation solid-organ recipients (DLBCL/PTLD; n = 21), were characterized histogenically as germinal center (GC) or non-germinal center (NGC). Expression of BAFF, BAFF-R, and NF-κB proteins p50 and p52 and the presence or absence of EBV were compared in these clinical contexts. Regardless of the GC or NGC pattern of DLBCL, BAFF-R was expressed in 37% of DLBCL/IC but in only 4.8% of DLBCL/PTLD. p52 was expressed in DLBCL/PTLD/NGC (12 of 19 cases) as compared with DLBCL/IC/NGC (0 of 18 cases). This pattern might be related to the presence of EBV and latent membrane protein 1 because p52 expression was observed primarily in EBV-positive DLBCL/PTLD cases expressing latent membrane protein 1. Thus, the activation profile or NGC pattern of DLBCL/PTLD was not associated with BAFF/BAFF-R expression, whereas nuclear p52 related to NF-κB2 pathway activation might be linked to EBV.     

Primary diffuse large B-cell lymphoma of the testis

In this short review, we discuss primary diffuse large B-cell lymphoma of the testis, an entity that is most commonly seen in older patients. The most common clinical presentation is a unilateral testicular mass. Microscopically, the tumor shows diffuse infiltration of lymphocytes between intact seminiferous tubules. Spermatogenic arrest, interstitial fibrosis, and tubular hyalinization are commonly seen. The tumor is positive for B-cell markers by immunohistochemistry. Treatment has traditionally been with orchiectomy and combination chemotherapy; however, only a minority of patients enjoy a prolonged disease-free survival. Differential diagnosis includes seminoma and viral and granulomatous orchitis.     

信号通路在弥漫性大B细胞淋巴瘤发病过程中的作用

弥漫性大B细胞淋巴瘤(DLBCL)是最常见的一种B细胞恶性肿瘤,约占成人非霍奇金淋巴瘤的30%～40%.依据肿瘤细胞起源大致可将DLBCL分为生发中心B细胞型(GCB型)及非生发中心B细胞型(非GCB型).B细胞发育过程中,多种信号通路精确地调控其细胞周期、增殖、分化及凋亡,以达到平衡,确保B细胞的正常发育及成熟.     

Expression of p63 in anaplastic large cell lymphoma but not in classical Hodgkin's lymphoma

Immunohistochemical determination of p63 protein is frequently used in the pathologic diagnosis of nonhematological solid tumors. In malignant hematological disease, p63 expression has been reported in 22% of follicular lymphoma, about 35% of diffuse large B-cell lymphoma, 23% of chronic lymphocytic leukemia, and in some cases of blast crisis of chronic myelogenous leukemia. Anaplastic large cell lymphoma is a rare disease that accounts for less than 5% of all cases of non-Hodgkin's lymphoma. There is little information concerning p63 expression in this specific type of lymphoma. In some cases, the morphological and phenotypic features between anaplastic large cell lymphoma and classical Hodgkin's lymphoma are similar, making this differential diagnosis challenging. We studied p63 expression using a tissue microarray approach in 154 cases of anaplastic large cell lymphoma, including 38% anaplastic large cell kinase positive and 62% anaplastic large cell kinase negative, and 58 Hodgkin's lymphoma cases. Sixty-eight cases of anaplastic large cell lymphoma (44%) showed p63 nuclear positivity (41% of anaplastic large cell kinase positive and 47% of anaplastic large cell kinase negative). Of 130 cases of systemic-anaplastic large cell lymphoma, 42% showed p63 positivity. The neoplastic cells expressed p63 in 38% of the cases of CD45-negative/anaplastic large cell kinase-negative null cell-type anaplastic large cell lymphoma, a subgroup that offers the most difficulties in the differential diagnosis with classical Hodgkin's lymphoma. In contrast, none of the cases of classical Hodgkin's lymphoma demonstrated any p63 expression. These results demonstrate that p63 protein expression is frequently expressed in a subset of anaplastic large cell lymphoma cases and may be used as a potential tool in the differential diagnosis between anaplastic large cell lymphoma and classical Hodgkin's lymphoma.     

Primary breast diffuse large B-cell lymphoma shows a non-germinal center B-cell phenotype.

Primary breast diffuse large B-cell lymphoma has a poor prognosis relative to other extranodal diffuse large B-cell lymphoma. Recently, diffuse large B-cell lymphoma has been subclassified as germinal center B-cell-like and nongerminal center B-cell types using tissue microarrays. The 5-year overall survival rate of the germinal center B-cell group is better than that of the nongerminal center B-cell group. To elucidate the reason for which primary breast diffuse large B-cell lymphoma has a poor clinical outcome, we investigated 15 patients with primary breast diffuse large B-cell lymphoma (stage IE; 13 cases, stage IIE; two cases) by immunohistochemistry using various markers including CD10, Bcl-6, MUM1 and MIB-1 and by molecular analysis of the immunoglobulin heavy chain gene variable region. Immunohistochemistry showed 0/15 (positive cases/examined cases) for CD10, 5/15 for Bcl-6, 15/15 for MUM1, 10/15 for Bcl-2, 2/15 for CD5 and 4/15 for CD40. The expression pattern of CD10(-) MUM1(+) in primary breast diffuse large B-cell lymphoma corresponded to the nongerminal center B-cell group. Moreover, the MIB-1 index was distributed from 60 to 95% with a mean of 79%, indicating a high proliferation of the lymphoma cells. The immunoglobulin heavy chain gene variable region of primary breast diffuse large B-cell lymphoma had a mutation frequency of 1-10% (seven cases) and 0-1 additional mutations in ongoing mutation analysis (five cases). Primary breast diffuse large B-cell lymphoma had characteristics of the nongerminal center B-cell group. In conclusion, primary breast diffuse large B-cell lymphoma has a nongerminal center B-cell phenotype and has a high MIB-1 index. These features might therefore be associated with poor prognosis.     

Genomic imbalances during transformation from follicular lymphoma to diffuse large B-cell lymphoma.

Follicular lymphoma is commonly transformed to a more aggressive diffuse large B-cell lymphoma (DLBCL). In order to provide molecular characterization of this histological and clinical transformation, comparative genomic hybridization was applied to 23 follicular lymphoma and 35 transformed DLBCL tumors from a total of 30 patients. The results were also compared with our published findings in de novo DLBCL. Copy number changes were detected in 70% of follicular lymphoma and in 97% of transformed DLBCL. In follicular lymphoma, the most common alterations were +18q21 (33%), +Xq25-26 (28%), +1q31-32 (23%), and -17p (23%), whereas transformed DLBCL most frequently exhibited +Xq25-26 (36%), +12q15 (29%), +7pter-q22 (25%), +8q21 (21%), and -6q16-21(25%). Transformed DLBCL showed significantly more alterations as compared to follicular lymphoma (P=0.0001), and the alterations -6q16-21 and +7pter-q22 were only found in transformed DLBCL but not in follicular lymphoma (P=0.02). Alterations involving +13q22 were significantly less frequent, whereas -4q13-21 was more common in transformed as compared to de novo DLBCL (P=0.01 and P=0.02, respectively). Clinical progression from follicular lymphoma to transformed DLBCL is on the genetic level associated with acquisition of increasing number of genomic copy number changes, with non-random involvement of specific target regions. The findings support diverse genetic background between transformed and de novo DLBCL.     

Higher frequency of p53 gene mutations in diffuse large B-cell lymphoma with MALT component

p53 gene mutation is not a frequent event in the tumorigenesis of lymphomas and the expression of p53 protein is independent of p53 gene mutations. The present study aimed to investigate mutations in the p53 gene in a series of extranodal B-cell lymphomas, and its association with p53 protein expression. A total of 52 cases were graded histologically into Grade 1, Grade 2 and Grade 3 tumors and p53 protein expression was detected using immunohistochemistry. Mutations in the p53 gene were analyzed using polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) and mobility shifts were confirmed by direct sequencing. The tumors comprised 26 (50%) Grade 1, 9 (17%) Grade 2 and 15 (29%) Grade 3. A high proportion of Grade 2 (25%) tumors expressed p53 protein (P = 0.051) and carried p53 gene mutation (33%) (P = 0.218). However, p53 protein expression was not associated with p53 gene mutations (P = 0.057). Transversion mutations (88%) were more frequently detected than transition mutations (12%). The present study revealed that p53 gene mutations and p53 protein expression occurred in higher frequencies in Grade 2 tumors, which may be of pathogenetic importance. The high frequency of transversion mutations may reflect the influence of an etiological agent in the tumorigenesis of mucosa-associated lymphoid tissue (MALT lymphoma).     

Expression of PKC-beta or cyclin D2 predicts for inferior survival in diffuse large B-cell lymphoma.

We sought to determine whether identification of poor-risk subgroups of diffuse large B-cell lymphoma (DLBCL) using immunohistochemical stains would have practical utility with regard to prognosis and therapeutic decisions. Tissue microarray blocks were created using replicate samples of formalin-fixed, paraffin-embedded tissue from 200 cases of de novo DLBCL. The sections were stained with antibodies to proteins that are expressed by activated or proliferating B cells including MUM1, FOXP1, bcl-2, survivin, protein kinase C-beta (PKC-beta), cyclin D2, cyclin D3, and Ki-67. In univariate analysis, tumor expression of cyclin D2 (P = 0.025) or PKC-beta (P = 0.015) was associated with a worse overall survival, whereas none of the other markers was predictive of overall survival. Patients with DLBCL that expressed either cyclin D2 or PKC-beta had a 5-year overall survival of only 30% as compared to 52% for those who were negative for both markers (P = 0.0019). In multivariate analysis, the expression of cyclin D2 or PKC-beta was an independent predictor of poor overall survival (P = 0.035). Cyclin D2 and PKC-beta expression will be useful in designing a 'biological prognostic index' for patients with DLBCL.