国外动态

鼻咽癌外周血ＥＢ病毒ＤＮＡ与转移和生存的关系台湾研究人员最近抽取１２４例无远处转移鼻咽癌患者和１１４例伴ＥＢ病毒感染的健康人群的外周血样 ,进行血浆和红细胞分离后 ,从红细胞中提取ＤＮＡ ,并用巢式ＰＣＲ检测ＥＢ病毒ＤＮＡ（ＥＢＮＡ １） ,所有病例均行放疗及化疗     

遗传性乳腺癌易感基因BRCA1在女性患者表达的研究

目的 探讨中国人群中乳腺癌与乳腺癌基因ＢＲＣＡ１的关系。方法 应用聚合酶链反应－单链构象多态性分析技术（ＰＣＲ－ＳＳＣＰ）和ＤＮＡ序列测定技术对上海地区５０例良笥乳腺肿瘤和２５例恶性乳腺肿瘤患者和香港地区１３０例乳腺癌患者进行了ＢＲＣＡ１基因表达的研究,并结合免疫组织化学分析其雌激素受体（ＥＲ）,孕激素受体（ＰＲ０水平。     

鼻咽癌EB病毒DNA检测和潜在膜蛋白表达的意义

应用ＰＣＲ技术和免疫组化ＳＰ法检测了４６例鼻咽癌组织中ＥＢ病毒ＤＮＡ、ＥＢ病毒潜在膜蛋白（ＬＭＰ－１）的表达。结果发现ＥＢ病毒ＤＮＡ检出率和ＬＭＰ－１的表达率分别为８０．４％和５３．３％，ＥＢ病毒ＤＮＡ检出率和ＬＭＰ－１表达与鼻咽癌组织学分级有关。提示ＥＢ病毒ＮＤＡ的存在和ＬＭＰ－１表达与细胞癌变关系密切     

乳腺肿瘤DNA含量及雌激素受体的测定

应用流式细胞分析仪检测乳腺癌（４２例）、乳腺纤维腺瘤（１０例）、乳腺囊性增生病（１０例）及正常乳腺组织（１０例）的细胞ＤＮＡ含量。４２例乳腺癌标本中，２６例（６２％）为异倍体ＤＮＡ；乳腺囊性增生病和正常乳腺组织均为二倍体ＤＮＡ。乳腺癌标本均行雌激素受体（ＥＲ）测定，１１例（２６％）为阴性。同时对所有乳腺癌进行有关临床资料和病理分析，发现乳腺癌ＤＮＡ含量与病人年龄及ＥＲ状态差异均有显著性意义（Ｐ＜０．０５）。乳腺肿瘤细胞周期分析发现异倍体癌Ｓ期细胞比率最高。通过乳腺癌细胞ＤＮＡ含量及ＥＲ测定，计算细胞增殖周期中各期细胞比率，可以判断乳腺癌生物学特性，为患者预后的评估提供客观、定量和可重复性参数，弥补形态学检查的不足，并对术后辅助治疗有指导意义。     

人乳头瘤病毒16、18型在乳腺癌组织中的表达

目的：探讨人乳头瘤病毒（ＨＰＶ）１６、１８型感染与人乳腺癌病因学的关系。方法：采用免疫组化法（ＳＰ）检测ＨＰＶ１６、１８Ｅ６蛋白在１０例正常乳腺组织,４５例乳腺癌组织中的表达并对癌组中１３例ＨＰＶ１６、１８Ｅ６蛋白阳性材料进行ＨＰＶ１６、１８ＤＮＡ原位杂交检测。结果：癌组中ＨＰＶ１６、１８Ｅ６阳性率为５３．３％（２４／４５）,而正常乳腺组织中均为阴性表达。ＨＰＶ１６、１８ＤＮＡ阳性率为３８．５％（     

乳腺肿瘤组织中C—erbB—2癌基因产物表达与雌,孕激素受体关系的初探

乳腺肿瘤组织中Ｃ─ｅｒｂＢ─２癌基因产物表达与雌、孕激素受体关系的初探陈发龙，覃思繁广西肿瘤防治研究所病理科（南宁市５３００２７）近年来多数学者的研究已证实，Ｃ－ｅｒｂＢ－２产物在乳腺癌中的高度表达以及ＥＲ、ＰＲ状态是判断乳腺癌预后的可靠指标。为此，...     

EB病毒感染与乳腺癌发病有关

EB病毒与恶性淋巴瘤、鼻咽癌、胃癌、肠癌、平滑肌肉瘤、子宫颈癌的发病有关，国内已有报道。上海医科大学肿瘤医院报告在乳腺癌中发现有EB病毒的DNA参入，证实EB病毒与乳腺癌发病有关。以许良中教授为首的研究小组应用多聚酶链反应（PCR）和免疫组织化学方法联合检测了1吸例乳腺癌病例和对冽乳腺良性疾患的用病毒感染情况，发现乳腺癌阳性率达28．4％，乳腺良性疾患的阳性率仅5．4％。PCR检测结果证实了EB病毒的基因组已整台至乳腺癌细胞的DNA中，免疫组织化学反应肯定了病毒阳性颗粒存在于乳腺癌细胞中而浸润的淋巴细胞和间质细胞…     

大肠肿瘤病变中CMV DNA的检测及其致病作用的初步探讨

大肠是恶性肿瘤及良性肿瘤的好发部位，如大肠癌、腺瘤和炎性息肉等。而大肠又是诸多病毒感染的器官之一，特别近年来国内实验报道了在大肠肿瘤病变中发现人疱疹病毒ＨＨＶ及ＥＢ病毒。为了探讨巨细胞病毒（ＣＭＶ）感染在大肠肿瘤中的检出率以及评估疱疹病毒对大肠肿瘤的致病作用。我们利用巢式ＰＣＲ技术在大肠肿瘤病变中对巨细胞病毒ＤＮＡ进行探测，结果如下。１材料与方法１．１标本种类 取经我院手术的大肠肿瘤患者的石蜡包埋组织块２０例，年龄３７～６４岁，平均５３岁。其中恶性病变８例，分别为：腺癌５例，炎性息肉恶变２例，绒…     

表皮生长因子受体及DNA含量在乳腺癌预测因素中的地位

用免疫组化法检测４６例乳腺癌组织中ＥＧＦＲ及ＥＲ，流式细胞技术检测ＤＮＡ倍体状况，结合病理因素及临床随访结果进行分析，结果发现：１）ＥＧＦＲ与ＥＲ呈显著负相关（Ｐ＜０．０５），与肿瘤组织学分级呈显著正相关（Ｐ＜０．０１），不同月经状况、肿瘤大小、淋巴结受累情况及ＴＮＭ分期中ＥＧＦＲ阳性率无显著差异，ＥＧＦＲ阳性患者生存期显著低于ＥＧＦＲ阴性患者的生存期；２）ＤＮＡ含量与ＥＲ呈负相关，与组织学分级，肿瘤大小及ＥＧＦＲ呈显著正相关，ＤＮＡ异倍体患者生存期明显低于二倍体肿瘤患者的生存期（Ｐ＜０．０１）。提示：ＥＧＦＲ、ＤＮＡ可作为乳腺癌预测预后的有效生物学信息。     

内皮素在乳腺癌组织中的免疫组织化学研究

近期国外研究发现，内皮素不单是一种缩血管物质，它对全身多种组织器官的细胞生长代谢都具有重要的生物学作用。作者应用免疫组织化学方法和图像分析技术观察４２例不同组织学分级的临床乳腺癌和８例正常乳腺组织中内皮素（ＥＴ－１）的定位分布与含量，结果表明：乳腺癌与正常乳腺组织呈ＥＴ－１标记阳性，阳性物质主要分布于细胞浆。乳腺癌对内皮素有较高比例的阳性表达，肿瘤细胞ＥＴ－１含量明显高于正常乳腺上皮细胞。在各级乳腺癌中，ＥＴ－１标记阳性率及其在阳性细胞中的含量，以Ⅲ级乳腺癌最高，Ⅱ级次之，Ⅰ级含量最低，即：肿瘤分化程度越低，ＥＴ－１含量越高。本研究较直观地反映出内皮素含量与乳腺组织的生长状态之间存在一种定量的关系。内皮素的过量增加，可能导致细胞恶性生长或恶性程度增高。     

Multiple oncogenic viruses are present in human breast tissues before development of virus associated breast cancer

Background

Multiple oncogenic viruses including, mouse mammary tumor virus, bovine leukemia virus, human papilloma virus, and Epstein Barr virus, have been identified as separate infectious pathogens in human breast cancer. Here we demonstrate that these four viruses may be present in normal and benign breast tissues 1 to 11 years before the development of same virus breast cancer in the same patients.

Methods

We combined the data we developed during investigations of the individual four oncogenic viruses and breast cancer. Patients who had benign breast biopsies 1–11 years prior to developing breast cancer were identified by pathology reports from a large Australian pathology service (Douglas Hanly Moir Pathology). Archival formalin fixed specimens from these patients were collected. The same archival specimens were used for (i) investigations of mouse mammary tumour virus (also known as human mammary tumour virus) conducted at the Icahn School of Medicine at Mount Sinai, New York and at the University of Pisa, Italy, (ii) bovine leukemia virus conducted at the University of California at Berkeley,(iii) human papilloma virus and Epstein Barr virus conducted at the University of New South Wales, Sydney, Australia.Seventeen normal breast tissues from cosmetic breast surgery conducted on Australian patients were used as controls. These patients were younger than those with benign and later breast cancer.

Results

Standard and in situ polymerase chain reaction (PCR) methods were used to identify the four viruses. The detailed methods are outlined in the separate publications.: mouse mammary tumor virus, human papilloma virus and Epstein Barr virus (Infect Agent Cancer 12:1, 2017, PLoS One 12:e0179367, 2017, Front Oncol 5:277, 2015, PLoS One 7:e48788, 2012).Epstein Barr virus and human papilloma virus were identified in the same breast cancer cells by in situ PCR.Mouse mammary tumour virus was identified in 6 (24%) of 25 benign breast specimens and in 9 (36%) of 25 breast cancer specimens which subsequently developed in the same patients.Bovine leukemia virus was identified in 18 (78%) of 23 benign breast specimens and in 20 (91%) of 22 subsequent breast cancers in the same patients.High risk human papilloma viruses were identified in 13 (72%) of 17 benign breast specimens and in 13 (76%) of 17 subsequent breast cancers in the same patients.Epstein Barr virus was not identified in any benign breast specimens but was identified in 3 (25%) of 12 subsequent breast cancers in the same patients.Mouse mammary tumour virus 3 (18%), bovine leukemia virus 6 (35%), high risk human papilloma virus 3 (18%) and Epstein Barr virus 5 (29%) were identified in 17 normal control breast specimens.

Conclusions

These findings add to the evidence that multiple oncogenic viruses have potential roles in human breast cancer. This is an important observation because evidence of prior infection before the development of disease is a key criterion when assessing causation.

     

Frequency of Epstein–Barr Virus DNA in Formalin-fixed Paraffin-embedded Tissue of Patients with Ductal Breast Carcinoma

Background: Ductal carcinoma is one of the most common breast cancer (BrC) among the women in the world.Several factors may involve in establishment of breast cancer. The role of viral infections have been investigated inBrC, Among them the association of Epstein Barr virus have been reported in the patients with breast cancer typeductal carcinoma. Thus this study was conducted to evaluate the rate of Epstein Barr virus in women with breast cancertype ductal carcinoma. Material and methods: A total of 72 formalin-fixed paraffin-embedded tissue blocks sampleswere collected from 37 (51.38%) women with breast cancer type ductal carcinoma and 35 (48.61%) samples of breastwith fibro adenoma as control group. The DNA was extracted for all the samples. The detection of EBNA 3C EBVDNA was done by nested PCR. The results of positive were sequenced to confirm PCR product and determine EBVgenotypes. Results: About 10/37 (27.02%) samples of ductal breast carcinoma were showed positive for EBNA 3CEBV DNA while 4/35 (11.42%) of fibro adenoma were positive for EBNA 3C EBV DNA (p= 0.095). Randomly 7PCR products were sequenced and the results of sequencing EBNA 3C shows, the detected EBVDNA were type 1EBV type. Conclusion: This study shows high prevalence of 27.02% EBV DNA type 1 was found in formalin-fixedparaffin-embedded tissue of Patients with ductal breast carcinoma. The outcomes of this study suggesting that EBVmight have a significant role in breast cancer in Ahvaz city, south west region of Iran. However the expression of EBVoncoproteins ,EBNA1, LMP1, and LMP2 require to be determined with ductal carcinoma cells. About 72.97% breastsamples showed negative for EBVDNA. The role other viruses including Human cytomegalovirus, papilloma virusesand Merkel viruses are required to be investigated in further studies.     

EB病毒诱发淋巴瘤中LMP的表达

背景与目的:EB病毒潜伏膜蛋白-1(latent membrane protein-1,LMP-1)是一种病毒癌蛋白,可能在淋巴瘤发生中起重要的作用.本文旨在了解EB病毒诱发的淋巴瘤细胞与正常人淋巴细胞中LMP的差异表达情况.方法:应用实时定量PCR方法检测EB病毒诱发淋巴瘤细胞和正常人淋巴细胞中LMP (LMP-1、LMP-2A及LMP-2B)的差异表达情况.采用Western blot检测LMP-1蛋白表达.结果:建立了EBV诱发淋巴瘤的动物模型获得诱发淋巴瘤,检测LMP-1、LMP-2A、LMP-2B在诱发淋巴瘤细胞及正常人淋巴细胞中的表达情况.实时定量PCR结果表明,LMP-1在诱发淋巴瘤细胞中的表达比在正常细胞中的表达上调255.7倍,表达差异有统计学意义(P＜0.05),LMP-2A在诱发淋巴瘤细胞中的表达比在正常细胞中的表达上调37.74倍,表达差异有统计学意义(P＜0.01),LMP-2B在诱发淋巴瘤细胞中的表达比在正常细胞中的表达上调330.63倍,表达差异有统计学意义(P＜0.05).Western blot结果表明LMP-1在诱发的淋巴瘤细胞中的表达比在正常淋巴细胞中的表达上调.结论:在EB病毒诱发的淋巴瘤发生过程中LMP可能起重要作用.     

HSG和MMP-3在不同乳腺组织中的表达

 目的探讨新的增殖抑制基因(hyperplasia suppressor gene,HSG)和基质金属蛋白酶-3(matrix metalloproteinase-3,MMP-3)在不同乳腺组织中的表达。方法应用免疫组化方法检测唐山市工人医院58例乳腺癌标本,33例乳腺纤维瘤标本,30例乳腺增生标本和15例正常乳腺组织标本HSG和MMP-3的表达。结果58例乳腺癌组织中HSG和MMP-3的表达率分别为44.83%(26/58)和84.48%(49/58),与正常乳腺组织和良性乳腺纤维腺瘤比较,乳腺癌组HSG表达率下降,MMP-3表达率升高,差异有显著性(P<0.05);乳腺癌组HSG低表达,与淋巴结转移有关(P<0.05),与肿瘤大小、年龄和临床病理分级无关,MMP-3高表达与肿瘤大小和淋巴结转移等无关。另外,在乳腺癌组、乳腺增生组、乳腺纤维腺瘤组和正常乳腺组织中,HSG与MMP-3无明显相关性。结论HSG和MMP-3在不同乳腺组织中表达量的不同,提示HSG和MMP-3与乳腺癌的发生、发展有着密切关系。     

RAR-β2 基因在乳腺肿瘤组织中的表达及意义*

目的:检测视黄酸受体β 2（RAR-β 2）基因在不同乳腺肿瘤组织中的表达,探讨RAR-β 2 基因与乳腺肿瘤的关系,分析其在乳腺癌发生、发展中的作用。方法:免疫组织化学法检测乳腺浸润性癌、导管上皮重度不典型增生、腺纤维瘤各40例及20例正常乳腺组织中RAR-β 2 的表达情况。RT-PCR 法检测乳腺浸润性癌、导管上皮重度不典型增生、腺纤维瘤及正常乳腺组织各20例RAR-β 2 的表达水平。结果:免疫组化结果显示,RAR-β 2 阳性表达主要位于细胞核,RAR-β 2 蛋白在乳腺浸润癌组织中阳性表达率（30.0%）明显低于正常乳腺组织（95.0%）,χ2=26.30,P<0.05。RAR-β 2 蛋白在乳腺重度不典型增生组织中阳性表达率（17.5%）低于乳腺癌组织,但差异无统计学意义（P>0.05）。 在乳腺浸润性癌组织中,RAR-β 2 表达与患者年龄、肿瘤大小、临床分期、腋下淋巴结转移状况、组织学分级、病理学类型以及ER、PR表达状况无相关性（P 均>0.05）。 随访结果显示,28例RAR-β 2 阴性乳腺癌患者中3 例发生内脏转移,而12例RAR-β 2 阳性患者仅1 例发生骨转移。RT-PCR 结果显示,RAR-β 2 在乳腺癌、导管上皮重度不典型增生、腺纤维瘤及正常乳腺组织中阳性表达率分别为25.0%（5/20）、35.0%（7/20）、85.0%（17/20）和100%（20/20）,乳腺癌组织RAR-β 2 mRNA 明显低于正常乳腺组织（χ2=30.43,P<0.001）。 结论:RAR-β 2 可能在乳腺癌的发生过程中发挥抑制作用,并且可能在乳腺癌发生的早期发挥作用。      

T- and B-cell clonality and frequency of human herpes viruses-6, -8 and Epstein Barr virus in angioimmunoblastic T-cell lymphoma

Angioimmunoblastic T-cell lymphoma (T-AIL) is a peripheral T-cell lymphoma of unknown etiology. Previous clonality studies have shown a heterogeneous composition of this disease with varying restrictions of B- and T-cell populations in the tumour. For the first time in a single study and in the same pathological materials, we have analysed, lymphoid cell clonality and occurrence of human herpes viruses and Epstein Barr virus. Of 18 cases 12 (66.6%) had clonal T- and three (16.6%) had clonal B-cells. Presence of the lymphotropic viral genome of HHV6 was detected in four of 18 lymph node biopsies from T-AIL patients (22%), all were TCRgamma clonal. No HHV8 were found. Epstein Barr genome was found in 40% of cases. There was no significant association between T-cell clonality and HHV-6 or EBV infection, or between B-cell clonality and any virus infection. We conclude that T-AIL is a biologically and clinically heterogeneous entity whose true nature remains to be clarified.     

Epstein-Barr Virus and Breast Cancer: Lack of Evidence for an Association in Iranian Women

Controversies regarding the role of Epstein-Barr virus (EBV) in breast cancer and lack of published literature in this regard in Iran, prompted us to assess EBV presence in 100 breast carcinoma and 42 control biopsies obtained from Iranian women. Breast carcinoma cases were comprised of 81 invasive ductal carcinoma NOS, 9 invasive lobular carcinoma, 1 apocrine carcinoma, 2 cribriform carcinoma, 2 papillary carcinoma and 5 mucinous carcinoma. Control biopsies consisted of 13 fibroadenoma, 9 benign epithelial proliferation (adenosis and sclerosing adenosis), 9 usual ductal hyperplasia, 4 atypical ductal hyperplasia, 4 non-proliferative fibrocystic changes and 3 normal breast tissue. To identify EBV-infected cells we applied immunohistochemical analysis, using monoclonal antibody against Epstein-Barr virus-encoded nuclear antigen 2 (EBNA-2) and latent membrane protein 1 (LMP-1). Further, polymerase chain reaction (PCR) was used to amplify EBV DNA, with primers that cover the EBV encoded RNA (EBER) and BamHIW regions. EBNA-2 and LMP-1 immunohistochemistry were negative in all breast cancer and control specimens. Using PCR, none of the 100 breast cancer samples or the 42 control specimens showed detectable EBV DNA. These results indicate that EBV may not play a significant role in the etiology of breast cancer in Iranian women.     

Identification of anti-Epstein-Barr virus (EBV) antibody signature in EBV-associated gastric carcinoma

Gastric Cancer - Around 10% of gastric carcinomas (GC) contain Epstein–Barr virus (EBV) DNA. We characterized the GC-specific antibody response to this common infection, which may provide a...     

Systemic treatment strategies and therapeutic monitoring for advanced nasopharyngeal carcinoma

Nasopharyngeal carcinoma (NPC) is endemic in Asia and is etiologically associated with the Epstein–Barr virus. Although radiotherapy can cure most patients with early-stage disease, those with advanced disease often develop recurrences following radiotherapy. The past decade has witnessed significant advances in the systemic treatment of advanced NPC. This article reviews the latest literature regarding: combined modality therapy for locoregionally advanced NPC; clinical trials of novel biologic and cytotoxic therapies for metastatic NPC; and disease monitoring with the plasma Epstein–Barr virus DNA assay.     

A novel application of plasma and cerebrospinal fluid level of epstein barr virus DNA in the diagnosis of leptomeningeal metastasis from nasopharyngeal carcinoma. A case report

Epstein Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC) is endemic in Southeast Asia, and the plasma level of EBV DNA is a highly sensitive marker of disease recurrence following radiotherapy. Leptomeningeal recurrence from NPC is extremely rare and difficult to diagnose; only 4 cases have been reported in the literature. We report a case of leptomeningeal recurrence in NPC that was diagnosed using imaging and plasma and cerebrospinal fluid EBV DNA assays, followed by a review of the literature.