经典型霍奇金淋巴瘤组织CD20和CD68表达临床意义的研究

目的:探讨CD20和CD68在经典型霍奇金淋巴瘤(CHL)组织中的表达及其与临床病理特征及预后的关系。方法:采用免疫组化方法检测29例CHL患者CD20和CD68的表达情况,并研究其与临床病理特征及预后的关系。结果:1)29例CHL中CD20和CD68的表达均与年龄有关(P=0.010,P=0.006),与性别、肿瘤分期、肿瘤分型、肿瘤大小、B症状等均无相关性,P>0.05。2)在CHL中CD20表达与CD68表达无相关性,r=-0.335,P>0.05。3)CD20高表达组5年无失败生存率高于低表达组(69.3%vs 54.5%),两组相比差异无统计学意义,P=0.610;CD68低表达组5年无失败生存率高于高表达组(86.3%vs 24.7%),两组相比差异有统计学意义,P=0.044。结论:1)CD20、CD68在CHL组织中表达均与年龄有关,与其他临床病理特征无关。2)在CHL中CD20表达与CD68表达无相关性。3)未能证实在CHL中CD20表达与预后具有相关性;CD68在CHL中表达与预后呈负相关。     

经典型霍奇金淋巴瘤组织CD20和0D68表达临床意义的研究

目的：探讨CD20和CD68在经典型霍奇金淋巴瘤（CHL）组织中的表达及其与临床病理特征及预后的关系。方法：采用免疫组化方法检测29例cHL患者CD20和cD68的表达情况,并研究其与临床病理特征及预后的关系。结果：1）29例cHL中CD20和cD68的表达均与年龄有关（P=0．010,P=0．006）,与性别、肿瘤分期、肿瘤分型、肿瘤大小、B症状等均无相关性,P〉0．05。2）在cHL中cD20表达与cD68表达无相关性,r=-0．335,P〉0．05。3）CD20高表达组5年无失败生存率高于低表达组（69．3％vs54．5％）,两组相比差异无统计学意义,P=0．610;CD68低表达组5年无失败生存率高于高表达组（86．3％vs24．7％）,两组相比差异有统计学意义,P=0．044。结论：1）CD20、CD68在CHL组织中表达均与年龄有关,与其他临床病理特征无关。2）在CHL中CD20表达与CD68表达无相关性。3）未能证实在CHL中CD20表达与预后具有相关性;CD68在CHL中表达与预后呈负相关。     

肺鳞状细胞癌伴神经内分泌分化与生物学特性及预后关系探讨

目的:初步探讨肺鳞状细胞癌的神经内分泌分化(neuroendocrine-like differentiation,ND)情况与生物学行为和预后的关系.方法:收集手术后经病理证实为肺原发鳞癌患者120例瘤组织石蜡标本,术前均未接受放化疗.采用免疫组化二步法检测神经元特异性烯醇化酶(NSE),突触素(SYN)和嗜铬素A(CGA)的表达,采用X2检验分析ND与肺鳞癌生物学行为之间的关系,分别采用kaplan-meier生存曲线和COX风险比例模型进行单因素和多因素生存分析.结果:120例肺鳞癌中,CGA阳性率46.7%,NSE阳性率60.8%,SYN阳性率36.7%.鳞癌伴ND阳性率为40.8%.相关性分析结果示3种标志物之间无明显相关性.肺鳞状细胞癌伴ND与肿瘤细胞分化程度及瘤体分期(T分期)有关,肿瘤细胞分化越差,瘤体分期越高,ND阳性率越高.SYN的阳性表达与患者的年龄、性别及肿瘤细胞的分化程度有关,年龄越高,女性,肿瘤细胞分化越差,SYN阳性表达率越高.单因素生存分析结果经Log-Rank检验示SYN(X2=3.961,P=0.047)及术后化疗(X2=4.447,P=0.035)与患者的术后生存率有关,而ND与患者术后生存率无明显相关性(X2=0.524,P=0.469).Cox多因素生存分析结果示患者的年龄(OR=0.459,P=0.029),SYN阳性表达(OR=2.114,P=0.036),CGA阳性表达(OR=0.558,P=-0.066)和术后化疗(OR=1.866,P=0.091)与患者预后相关,可作为可切除肺鳞癌患者的独立预后因素.结论:肺鳞癌伴神经内分泌分化与肿瘤细胞分化程度及瘤体分期有关,SYN和术后化疗是评价可手术患者预后的两个重要指标.     

血管免疫母细胞性T细胞淋巴瘤中CD200和可诱导共刺激分子的表达及意义

目的:探讨CD200和可诱导共刺激分子（ICOS）蛋白在血管免疫母细胞性T细胞淋巴瘤（AITL）中的表达情况、与预后的关系及其在AITL鉴别诊断中的意义。方法:选择郴州市第一人民医院、郴州市第四人民医院、湘南学院附属医院及郴州市第三人民医院2012年6月至2019年12月39例AITL患者和郴州市第一人民医院2016年8月至2019年7月诊断为经典霍奇金淋巴瘤（CHL）及非特指型外周T细胞淋巴瘤（PTCL-NOS）患者各10例。免疫组织化学法检测CD200、ICOS、CD10、程序性死亡受体1（PD-1）、bcl-6及CXC趋化因子配体13（CXCL13）蛋白表达情况,分析CD200、ICOS蛋白与AITL患者的临床病理特征及预后的关系,及二者在AITL与PTCL-NOS、CHL鉴别诊断中的意义。结果:39例AITL患者中CD200、ICOS蛋白阳性率分别为71.79%（28/39）、61.54%（24/39）;10例CHL患者中CD200弱至中等阳性7例,ICOS蛋白均为阴性;10例PTCL-NOS患者中,CD200阳性4例,ICOS蛋白阳性1例;AITL患者与CHL、PTCL-NOS患者间ICOS蛋白阳性率比较,差异均有统计学意义（均 P<0.05）;AITL患者与CHL、PTCL-NOS患者间CD200蛋白阳性率比较,差异均无统计学意义（χ 2=0.013, P=0.911;χ 2=3.551, P=0.060）。乳酸脱氢酶（LDH）升高及国际预后指数（IPI）评分为3~4分的AITL患者CD200阳性率高于相应的LDH正常和IPI评分0~2分患者（均 P<0.05）;LDH升高及PD-1阳性AITL患者ICOS阳性率高于相应的LDH正常和PD-1阴性患者（均 P<0.05）。CD200阳性与阴性AITL患者3年总生存（OS）率（4.2%比66.7%）和3年无进展生存（PFS）率（5.3%比77.1%）比较,差异均具有统计学意义（均 P<0.01）;ICOS蛋白阳性与阴性AITL患者3年OS率（15.3%比38.6%）比较,差异具有统计学意义（ P=0.011）,两组间3年PFS率（18.6%比41.5%）比较,差异无统计学意义（ P=0.059）。多因素分析结果显示,CD200（ HR=0.076,95% CI 1.555~79.497, P=0.001）、结外是否受累（ HR=11.117,95% CI 1.555~79.497, P=0.016）、LDH（ HR=2.147,95% CI 0.844~5.459, P=0.109）是AITL患者OS的独立影响因素;CD200（ HR=0.075,95% CI 0.016~0.357, P=0.001）、LDH（ HR=2.335,95% CI 0.929~5.870, P=0.071）是AITL患者PFS的独立影响因素。 结论:CD200和ICOS可以作为AITL辅助诊断的指标,ICOS蛋白有助于AITL与CHL、PTCL-NOS的鉴别。CD200可以作为判断AITL患者预后和病情恶化的指标。     

鼻咽癌组织中MMP-9 CD44v6蛋白表达的检测及其临床意义

目的:探讨鼻咽癌组织中MMP-9、CD44v6蛋白表达与鼻咽癌侵袭转移和患者预后的关系.方法:采用免疫组化ISAB法检测100例存档、石蜡包埋鼻咽癌组织中MMP-9、CD44v6蛋白表达,并分析其与各临床指标和患者总生存率之间的关系.结果:鼻咽癌组织中MMP-9蛋白表达阳性率为85.0%(85/100),其中( )23.0%,( )53.0%,( )9.0%.CD44v6蛋白表达阳性率63.5%(60/96),其中( )37.5%,( )8.3%,( )16.7%.MMP-9表达( )的鼻咽癌患者总生存率显著低于MMP-9表达(-)、( )、( )的患者.CD44v6表达为(-)、( )、( )、( )的各组鼻咽癌患者之间的总生存率无差异.鼻咽癌组织中MMP-9和CD44v6表达与患者年龄、性别、T分期、N分期及92'分期无关.结论:鼻咽癌组织中MMP-9、CD44v6蛋白表达与患者年龄、性别、颈淋巴结转移无关.MMP-9蛋白表达强阳性提示患者预后差.     

1～3个腋淋巴结阳性的T1～T2期乳腺癌改良根治术后患者预后因素分析

目的:分析和研究影响T1～T2期伴1～3个腋淋巴结阳性的乳腺癌改良根治术后患者的预后因素。方法:研究对象为2001年1月—2006年9月接受乳腺癌改良根治术的、有1～3个腋淋巴结阳性的434例T1～T2期乳腺癌患者,其中238例未行术后放疗,196例患者行术后放疗。放疗范围为胸壁+同侧锁骨上野区,总剂量为46～50Gy/23～25次。计算全组患者的3年和5年总生存率、局部控制率和无病生存率,并对影响总生存、局部控制率和无病生存率的因素进行单因素和多因素分析。结果:全组患者的3年和5年总生存率分别为94.7%和85.7%,3年和5年局部控制率分别为96.5%和95.6%,3年和5年无病生存率分别为89.3%和82.3%。单因素分析显示,年龄(P=0.008)和放疗(P=0.039)是影响总生存的预后因素,放疗(P=0.041)是影响局部控制率的预后因素,年龄(P=0.000)、淋巴结阳性数(P=0.037)和放疗(P=0.047)是影响无病生存率的预后因素。多因素分析显示,年龄(P=0.011)是影响总生存的独立预后因素,阳性淋巴结数(P=0.040)和放疗(P=0.020)是影响局部控制率的独立预后因素,年龄(P=0.002)、阳性淋巴结数(P=0.013)和放疗(P=0.039)是影响无病生存率的独立预后因素。结论:术后放疗可提高1～3个腋淋巴结阳性的T1～T2期乳腺癌患者的局部控制率、总生存率和无病生存率。年龄36～50岁患者的预后最好。T1～T2期有1～3个腋淋巴结转移的乳腺癌改良根治术后患者,其阳性淋巴结数越多,预后越差。放疗范围包括胸壁和锁骨上区是可行的。     

内皮素受体A表达与鼻咽癌预后的关系

背景与目的:内皮素受体A(endothelin A receptor,ETAR)激活参与肿瘤的生长及转移,包括细胞增殖、细胞凋亡、血管生成与肿瘤转移等作用。本研究探讨鼻咽癌组织中ETAR的表达与临床特征及预后的关系。方法:采用ETAR单克隆抗体对153例鼻咽癌组织中ETAR的表达进行免疫组化SABC技术检测。结果:鼻咽癌ETAR的阳性率为73.9%。ETAR的表达与性别、年龄、T分期、N分期及临床TNM分期无明显相关性(P>0.05)。ETAR阴性组和阳性组的3年总生存率分别为87.5%和73.2%(P=0.029),3年无瘤生存率分别为80.0%和57.3%(P=0.009),3年无局部区域复发生存率分别为86.9%和80.2%(P=0.228),3年无远处转移生存率分别为89.9%和70.4%(P=0.012)。Cox模型多因素分析显示ETAR表达、性别、年龄、T分期和N分期是影响总生存、无瘤生存及远处转移的独立预后因素。结论:ETAR的表达与鼻咽癌患者的远处转移风险有关,其高表达提示患者预后不良。     

肿瘤浸润淋巴细胞在食管癌组织中表达及与预后的关系

目的:研究食管癌组织中浸润的CD3+T、CD8+T、颗粒酶B(granzyme B,GrB)阳性T细胞和Foxp3+调节性T细胞(regulatory T cell, Treg)表达情况及对预后的影响.方法:应用免疫组织化学法检测CD3、CD8、GrB和Foxp3在90例食管癌间质和癌巢中的表达,计数阳性细胞,应用Cox回归模型和Kaplan-Meier生存曲线分析其与患者预后的关系.结果:本组病例3年总生存率为66.67%(60/90).单因素生存分析表明,食管癌间质和癌巢中CD3+T、CD8+T细胞高表达组3年生存率高于低表达组,差异有统计学意义(P<0.05);GrB+T细胞高表达组较低表达组有生存优势,但差异无统计学意义(P>0.05);Foxp3+Treg细胞高表达组生存率低于低表达组,差异有统计学意义(P<0.05).Cox模型多因素分析表明,食管癌间质浸润的CD3+T、CD8+T 、Foxp3+Treg细胞数量、病变长度和TNM分期均是影响生存期的独立因素(均P<0.05) .结论: 间质浸润的CD3+T、CD8+T细胞增多时患者预后良好,Foxp3+Treg细胞数量增多则预后不良.     

CD168在胃癌组织中的表达及预后意义

目的 探讨胃癌组织中透明质酸介导的细胞游走受体(CD168)的表达情况与各临床病理因素及其预后的关系,评估其在胃癌侵袭转移过程中的作用及预测胃癌患者预后的价值.方法 采用免疫组织化学法检测72例胃癌组织和26例正常胃黏膜组织中CD168的表达情况.同时评估CD168的表达与临床病理因素(年龄、性别、组织学、肿瘤浸润深度、淋巴结转移和临床分期)之间的关系.用Kaplan-Meier法评估胃癌患者术后5年生存率.结果 胃癌组织中CD168阳性表达率为58.3％,与正常胃黏膜中的阳性表达率(19.2％)比较,差异有统计学意义(P=0.001);CD168阳性表达率与肿瘤分化程度(P=0.001)、淋巴结转移(P=0.003)、临床分期等(P=0.020)有显著相关性.CD168阳性表达率与年龄、性别、肿瘤大小和肿瘤浸润深度无显著相关性.胃癌患者的生存期分析显示,CD168阴性组5年生存率(67.2％)显著高于CD168阳性组5年生存率(29.8％),两组间差异有统计学意义(P=0.01).结论 CD168高表达与胃癌的浸润和转移密切相关,可以作为预测胃癌预后的一个生物学指标.     

弥漫大B细胞淋巴瘤survivin表达与临床预后关系探讨

目的:探讨弥漫大B细胞淋巴瘤survivin表达与临床表现的关系.方法:收集本院自1997年至1999年的初治弥漫大B细胞淋巴瘤共63例,均接受治疗并进行随访.用免疫组化SP法检测其survivin表达情况.应用SPSS10.0软件行生存分析并对各临床指标与预后的关系进行单因素和多因素分析.结果:63例弥漫大B细胞淋巴瘤病例中有43例survivin表达阳性,阳性率为68.3%,其表达与性别、年龄、分期、结外病灶数目无明显相关关系,与PS、LDH、B症状、IPI显著相关(P<0.05).其5年总生存率为50.04%.survivin表达阳性的弥漫大B淋巴瘤患者的总生存率明显低于survivin表达阴性患者(P=0.000 1),二者的5年生存率分别为30.36%和90%.多因素分析显示,survivin表达是弥漫大B细胞淋巴瘤的独立预后指标.结论:survivin是弥漫大B细胞淋巴瘤的一个极有价值的预后指标,与IPI结合可于早期筛选出常规治疗预后不良的病例,有助于指导治疗及改善预后.     

CD20 expression in Hodgkin and Reed-Sternberg cells of classical Hodgkin's disease: associations with presenting features and clinical outcome.

PURPOSE: CD20 can be expressed in Hodgkin and Reed-Sternberg (HRS) cells of classical Hodgkin's disease (HD), but its clinical significance remains controversial. Therefore, we correlated CD20 expression with presenting features and clinical outcome of untreated patients with classical HD. PATIENTS AND METHODS: Patients were eligible if they were previously untreated and human immunodeficiency virus-1 negative, had biopsy-proven classical HD, and if pretreatment paraffin-embedded tumor tissue was available. CD20 expression was determined by immunohistochemistry without knowledge of clinical outcome. A tumor was considered positive if any HRS cells expressed CD20, but other cutoffs for number of CD20-positive HRS were also investigated. RESULTS: We identified 598 patients whose median age was 30 years and of whom 55% were male. HRS cells expressed CD20 in 132 (22%) of 598 patients with classical HD. When any percentage of CD20 expression in HRS cells was used as a cutoff, the 5-year failure-free survival (FFS) for positive versus negative tumors was 86% versus 84%, respectively, for 302 patients treated with doxorubicin, bleomycin, vinblastine, and dacarbazine or equivalent regimens (P =.7 by log-rank test), 74% versus 77%, respectively, for 181 patients treated with mitoxantrone, vincristine, vinblastine, and prednisone and radiotherapy (P =.7 by log-rank test), 74% versus 84%, respectively, for 54 patients treated with MOPP (P =.4 by log-rank test), and 77% versus 88% for 53 patients treated only with radiotherapy (P =.5 by log-rank test). The 5-year FFS was not statistically different when cutoffs of 5% up to 50% for CD20-positive HRS cells were used. CONCLUSION: CD20 is expressed by HRS cells in 22% of patients with classical HD but is not associated with different FFS after treatment with equivalent regimens.     

Bortezomib induces caspase-dependent apoptosis in Hodgkin lymphoma cell lines and is associated with reduced c-FLIP expression: a gene expression profiling study with implications for potential combination therapies

The Hodgkin cells and Reed-Sternberg cells (HRS) of classical Hodgkin lymphoma (CHL) are derived from germinal center B cells. The pathogenesis of CHL is unclear but constitutive activation of NFkappaB may contribute. Proteasome inhibition aimed at inhibiting NFkappaB has been shown to result in apoptosis in HRS cells. Here we investigated the effects of bortezomib, a proteasome inhibitor, in HRS cells with a combination of functional assays and gene expression profiling (GEP). Exposure of KMH2 and L428 cells to bortezomib resulted in inhibition of proliferation and induction of apoptosis. Gene expression analysis of KMH2 cells by oligonucleotide cDNA microarrays showed that a limited set of genes were differentially expressed involving several key cellular pathways including cell cycle and apoptosis. Among them, the caspase 8 inhibitor cFLIP was down-regulated and confirmed by Q-PCR. Given the evidence that cFLIP in HRS cells contribute to cells' insensitive to death receptor-mediated apoptosis, we combined bortezomib and TRAIL. This combination caused further down-regulation of cFLIP protein and increased apoptosis in CHL cells demonstrated by PARP p85 immunohistochemistry and immunoblotting. Such apoptotic effects were inhibited by caspase inhibitor z-VAD-FMK, confirming the pro-apoptotic effects of bortezomib and TRAIL are caspase-dependent. Bortezomib has no detectable effect on expression of TRAIL receptor DR4/DR5 in these two cell lines. Tissue microarray analysis of primary Hodgkin lymphomas displayed that 82% cases (95/116) expressed cFLIP in Reed-Sternberg cells. The discovery of apoptotic pathways that can be manipulated by proteasome inhibition provides rationale for the combination of bortezomib and agents such as TRAIL in CHL treatment.     

A clinicopathological study of nm23-H1 expression in classical Hodgkin’s lymphoma

BackgroundWe carried out immunohistochemistry to examine the expression of nm23-H1 in Hodgkin and Reed–Sternberg cells in patients with classical Hodgkin’s lymphoma (CHL).Patients and methodsWe evaluated 128 patients with CHL [87 patients with nodular sclerosis (NS) and 41 patients with mixed cellularity (MC)] for CD15, CD20, Ki-67, EBER, TIA-1, and nm23-H1 by immunohistochemistry.ResultsCD15 was expressed in 79%, CD20 in 11%, Ki-67 in 93%, EBER in 34%, TIA-1 in 11%, and nm23-H1 in 60% of the CHL patients. NS patients showed a significantly higher rate of nm23-H1 expression than MC patients (P < 0.001). The serum nm23-H1 level was significantly higher in patients with positive nm23 expression. Univariate analysis showed that stage IV, poor performance status, low hemoglobin level, low serum albumin level, age of 45 years or older, TIA-1-positive status, and nm23-H1-positive status were associated with significantly shorter progression-free survival. Multivariate analysis with these factors showed TIA-1 and cytoplasmic nm23-H1 expression to be significant and independent prognostic factors.ConclusionsOur results indicate that nm23-H1 expression is a prognostic factor for CHL and that it is as important as serum nm23-H1, both of which are useful for planning the treatment strategy.     

Hodgkin's lymphoma: the role of cell surface receptors in regulation of tumor cell fate

The hallmark of Hodgkin's lymphoma (HL) are mononucleated Hodgkin's cells and multinucleated Reed-Sternberg (HRS) cells, which usually account for only about 1% of cells in the tumor tissue. The majority of HRS cells in classical HL are derived from germinal centre B cells that have acquired disadvantageous Ig variable chain gene mutations and escaped from apoptosis. Due to reprogramming of gene expression, these lymphoma cells have lost the expression of most B-cell specific genes and acquired expression of multiple genes that are typical for other hematopoietic cells. HRS cells attract various cells of immune system into lymphoma tissue resulting in an inflammatory microenvironment. Moreover, HRS cells are dependent on microenvironment, especially on survival signals from other cells. Despite the loss of BCR?- the master-regulator of B cell fate, HRS cells express a number of receptors that regulate tumor cell survival. The rescue of HRS cells from apoptosis is a key event in HL pathogenesis. These cells express at least six receptors that belong to TNF receptor family: CD30, CD40, CD95, TACI, BCMA and RANK, co-stimulatory receptors CD80 and CD86, and E-selectins ligand CD15. Due to the mutations in genes encoding proteins of CD95-mediated apoptotic signaling pathway, it is not functional in HRS cells. Ligands of TNF family receptors on cells in HL microenvironment contribute to the activation of canonical and non-canonical NF-κB signaling pathways and survival program of HRS cells. Moreover, in HRS cells a number of multiple mutations in negative NF-κB regulators, and also gains and amplifications of positive regulators, cooperate in deregulating these pathways. All TNF receptors may be linked to the activation of prosurvival gene expression programs via Akt and ERK pathways. HRS cells also express CD150 receptor with specific ITSM motifs in the cytoplasmic tail. Ligation of this receptor on HRS cells induced activation of Akt and ERK pathways, and moreover, it triggered activation of JNK signaling cascade. Conclusion: The review presents the current views on the role of cell surface receptors in maintenance of HL microenvironment favorable for HRS cells survival.     

Prognostic significance of CD20 expression in classical Hodgkin lymphoma: a clinicopathological study of 119 cases.

PURPOSE: Recent evidence has demonstrated that classical Hodgkin lymphoma (cHL) originates from mature germinal center B cells. However, only approximately 25% of cHLs express the classical B-cell marker CD20. There is very little, and controversial, information on the prognostic significance of CD20 expression in cHL with regard to failure-free (FFS) and overall survival (OS). EXPERIMENTAL DESIGN: CD20 expression was investigated in a series of 119 cases of cHL treated at a single institution where complete clinical follow-up was available. The results were correlated to FFS and OS by the Kaplan-Maier method and uni- and multivariate analyses. RESULTS: Hodgkin and Reed-Sternberg cells expressed CD20 in 20% (24 of 119) of the cases based on a cutoff of 10% positivity. Within a mean follow-up period of 12 years, univariate analysis revealed a significantly higher frequency of disease relapses in the CD20-negative group (30 of 95; 32%) compared with CD20-positive tumors (2 of 24; 8%; P = 0.022). Compared by the log-rank test, the mean FFS in CD20-negative cases (202 months) was considerably shorter than in the CD20-positive cases (286 months; P = 0.0195). In a multivariate analysis, CD20 expression was an independent positive prognostic factor for FFS in cHL patients treated from 1974 to 1980 (P = 0.035). This effect disappeared in the period from 1981 to 1999 (P = 0.266). CONCLUSION: CD20-positive cHL shows a trend for better FFS and OS. However, improved treatment modalities seem to abolish these differences.     

Typing the histogenetic origin of the tumor cells of lymphocyte-rich classical Hodgkin's lymphoma in relation to tumor cells of classical and lymphocyte-predominance Hodgkin's lymphoma

Hodgkin's lymphoma (HL) is separated into the classical (c) and lymphocyte-predominance (lp) forms. Whereas classical Hodgkin-Reed/Sternberg (HRS) cells carry mutated immunoglobulin (Ig) gene rearrangements that are often "crippled" and lack intraclonal diversity, and are likely derived from preapoptotic germinal center (GC) B cells, the lymphocytic and histiocytic cells of lpHL are presumably derived from selected GC B cells and often show ongoing somatic hypermutation. The recently identified lymphocyte-rich classical (lrc) HL is characterized by HRS cells with the immunophenotype of classical HRS cells (CD30(+)CD15(+)CD20(-)CD45(-)) but an infiltrate similar to lpHL and a clinical behavior resembling lpHL. To identify the histogenetic origin of the HRS cells in lrcHL and to determine the relationship to the lymphoma cells of cHL and lpHL we characterized seven cases of lrcHL by immunohistochemistry and sequenced the rearranged Ig genes of single micromanipulated HRS cells. The expression patterns of BCL6, CD138, Oct2, and BOB1 in HRS cells of lrcHL showed differences to those of both cHL and lpHL. Analyses of rearranged Ig genes identified clonal HRS cell expansions carrying mutated Ig rearrangements without significant intraclonal diversity in all seven of the cases. In two cases crippling mutations, rendering originally functional V gene rearrangements nonfunctional, were observed. Thus, the mutation pattern of rearranged Ig genes of HRS cells in lrcHL is clearly different from those in lymphocytic and histiocytic cells of lpHL, and resembles the pattern in HRS cells of cHL, suggesting that HRS cells in lrcHL derive from (preapoptotic) GC B cells that silenced hypermutation. In one case in addition to the dominant HRS cell clone, CD30(+) EBV-infected HRS-like cells unrelated to the tumor clone were observed, suggesting development of an expanded population of EBV-harboring HRS-like cells in the microenvironment of HL.     

经典型霍奇金淋巴瘤组织中CSF-1R蛋白和FOXP3的表达及其与预后的相关性

目的观察叉头转录因子3(FOXP3)、集落刺激因子1受体(CSF-1R)蛋白在经典型霍奇金淋巴瘤(CHL)中的表达,并探讨其与患者预后的相关性。方法分析45例CHL患者的临床资料,包括临床特征、预后因素及治疗方案等。收集45例CHL患者的标本,采用免疫组织化学染色法检测FOXP3、CSF-1R的表达,并采用原位杂交技术检测EB病毒(EBV)及EBV编码的小mRNA(EBER)。结合患者临床及随访资料分析FOXP3、CSF-1R蛋白表达与预后的相关性。采用Kaplan-Meier法进行生存分析,Cox比例风险模型进行多因素分析。结果45例CHL患者中FOXP3高表达者23例(51.1%),CSF-1R阳性者18例(40.0%)。单因素分析结果显示,FOXP3、CSF-1R蛋白的表达、国际预后指数(IPI)评分、Ann Arbor分期以及EBER是影响患者5年总生存(OS)的预后因素;IPI评分、FOXP3蛋白的表达以及EBER是影响患者5年无进展生存(PFS)的预后因素。多因素分析结果则显示,CSF-1R蛋白的表达是影响患者5年OS的独立预后因素(HR:8.918,P=0.020),FOXP3蛋白的表达是影响患者5年PFS的独立预后因素(HR:0.122,P<0.001),且EBV是影响CHL患者PFS、OS的独立预后因素。结论微环境相关的预后因子FOXP3和CSF-1R及EBV均与CHL患者的预后相关,对CHL患者的预后具有一定判断作用,同时也可为CHL的靶向治疗提供新思路和理论依据。     

Does Rituximab Have a Place in Treating Classic Hodgkin Lymphoma?

Monoclonal antibodies targeting surface proteins on the malignant Hodgkin and Reed-Sternberg (HRS) cells are currently under intensive investigation with promising early results. Of particular interest is the CD20 antigen, because it is expressed not only on a small fraction of HRS cells but also on the benign reactive B cells in the microenvironment. The rationale of using rituximab in classic Hodgkin lymphoma (cHL) comprises several points: 1) HRS cells infrequently express CD20; 2) elimination of CD20-positive reactive B cells supporting HRS cells would deprive the malignant cells of survival signals; 3) elimination of reactive B cells may also potentially increase host immune response against HRS cells; 4) HRS stem cells express CD20. Although this rationale has not generally been confirmed in patients, promising results in managing cHL have occurred in early-phase clinical trials of rituximab, including trials of rituximab as a single agent in refractory or recurrent cHL, rituximab plus gemcitabine in refractory or recurrent cHL, and rituximab plus ABVD in newly diagnosed cHL. Based on the results of these trials, several prospective clinical trials using rituximab in the management of advanced-stage cHL and early-stage cHL are ongoing. These trials further clarify the role of rituximab in cHL. Enrollment of patients with this “classic” disease in clinical trials is encouraged.