EB病毒对人胚鼻咽上皮细胞的转化

为观察EBV和／或促癌物四癸酸佛波醇二酯（TPA）对其的转化作用，以人胚鼻咽上皮作体外原代组织培养，采用自B95－8细胞分离的EB病毒直接感染或结合TPA处理体外培养的人胚鼻咽上皮细胞，着重观察感染细胞在半固体培养基中的集落形成率；并采用PCR扩增法探讨EB病毒是否直接进入鼻咽上皮细胞。结果显示：单独EB病毒或灭活（56℃，30分钟）EB病毒加TPA感染时，病毒不能进入细胞导致表型改变；活性EB病毒结合TPA同时处理或先用EB病毒后用TPA处理时，EB病毒能直接进入细胞并导致细胞集落形成率明显增高（P＜0．05）。从而表明EB病毒体外能部分转化人胚鼻咽上皮细胞，其转化作用依赖于TPA的存在和病毒基因组的完整。     

鼻咽癌中EB病毒LMP1基因的序列变异

目的 检测广州地区鼻咽癌中EB病毒LMP1基因N-和C-末端区序列变异的热点,并探讨其产生的机制。方法 收集中山大学肿瘤医院未经治疗的鼻咽癌患者鼻咽新鲜活检标本63例。采用巢式聚合酶链反应（PCR）扩增EB病毒LMP1基因N-和C-末端区,用XhoⅠ对N-末端区扩增产物进行酶切分析,并检测C-末端区扩增产物30bp缺失的情况。采用四色荧光末端终止法对4例患者N-和C-末端区的8份扩增产物进行序列分析。结果 63例鼻咽癌组织EB病毒LMP1基因N-和C-末端区有4种序列变异类型：wt-XhoⅠ／wt-LMP1（4例,6．3％）、wt-XhoⅠ＆XhoⅠ-loss／del-LMP1（4例,6．3％）、wt-XhoⅠ／del-LMP1（5例,7．9％）和XhoⅠ-loss／del-LMP1（50例,79．5％）。序列分析显示：与B95-8细胞相比较,所有检测的鼻咽癌组织中EB病毒LMP1基因均发生了错义点突变和无义点突变。错义点突变数与无义点突变数之间的比值为2．25（9／4）。结论 广州地区鼻咽癌中EB病毒LMP1基因的序列变异类型以XhoⅠ-loss／del-LMP1占主导。LMP1基因N-末端区XhoⅠ酶切位点的丢失很可能是在C-末端区30bp缺失的基础上发生的。LMP1基因的4种序列变异类型可能代表了鼻咽癌变过程中EB病毒在宿主内演变的4个时相。     

EB病毒基因组限制片段长度多态性(RFLP)在鼻咽组织中的分布

利用PCR和限制性内切酶分析,探讨了EB病毒基因组限制片段长度多态型(RFLP)在正常鼻咽组织,鼻咽癌组织和口腔上皮脱落细胞中的分布情况。结果表明在正常鼻咽组织的EB病毒感染是一种普遍现象并且感染可能发生在癌变前;EB病毒基因组BamHF区的RFLP在鼻咽癌组织和正常的鼻咽组织之间有不同的分布;不同EB病毒RFLP变型(variant)的混合感染在正常咽组织比在癌组织中普遍,这结果表明可能在癌变发展过程中,由于部分带有EB病毒的细胞的选择生长,结果使得癌组织中的细胞以一种EB病毒变型为主;本文探讨了EB病毒的RFLP变型在鼻咽组织和口腔上皮脱落细胞分布的关系,这种关系可能为鼻咽癌高发区的癌变检测提供一种简单可靠的方法。     

良,恶性鼻咽活检组织中EB病毒DNA检测,EBNA的分…

应用ＥＢ病毒ＤＮＡＢａｍＨＩＷ片段，ＥＢＮＡ－２Ａ，Ｂ型分子探针，检测我区鼻咽癌（包括鼻咽原位癌），临床高度怀疑鼻咽癌（包括鼻咽上皮细胞非典型增生，颈淋巴结肿大及鼻咽结节）和慢性鼻咽炎等活检组织共９６例。各组均以Ａ型病毒感染为主：鼻咽癌组织性为２７／３５（７７．１％）。临床疑癌组７／１０（７０．０％）；慢性鼻咽炎组１８／２７（６６．７％）。Ｗ和Ａ型均阳性的鼻咽癌组为２０／２９（６９．０％）；非癌组     

EB病毒分子免疫学研究进展

1964年Epstein和Barr首次成功地将Burkitt非洲儿童淋巴瘤细胞通过体外悬浮培养建立病毒株，并在该病毒株细胞涂片中用电镜观察到疱疹病毒颗粒，命名为EB病毒（Epstein—Barr virus，EBV）。EBV与多种人类恶性肿瘤有关，研究发现EBV除引起Burkitt’s淋巴瘤、霍奇金病、非霍奇金淋巴瘤、鼻咽癌及NK／T淋巴细胞瘤之外，还与平滑肌肉瘤及胃、乳腺、肺等部位的恶性上皮肿瘤发病有关。EBV致癌谱的扩大使得对其致癌机制的研究具有更广泛的意义。     

良、恶性鼻咽活检组织中EB病毒DNA检测、EBNA的分型及表达

应用ＥＢ病毒ＤＮＡＢａｍＨＩＷ片段、ＥＢＮＡ一２Ａ、Ｂ型分了探针，检测我区鼻咽癌（包括鼻咽原位癌）、临床高度怀疑鼻咽癌（包括鼻咽上皮细胞非典型增生、颈淋巴结肿大及鼻咽结节）和慢性鼻咽炎等活检组织共９６例。各组均以Ａ型病毒感染为主：鼻咽癌组阳性为２７／３５（７７．１％）；临床疑癌组７／１０（７０．０％）；慢性鼻咽炎织１８／２７（６６．７％）。Ｗ和Ａ型均阳性的鼻咽癌组为２０／２９（６９．０％）；非癌组为８／２５（３２．０％）。同时用抗补体免疫荧光法检测ＥＢＮＡ的表达，鼻咽癌组阳性为１９／２０（９５．０％），而慢性炎组为１／１５（６．７％）。以ＥＢ病毒ＤＮＡＢａｍＨＩＷ片段、ＥＢＮＡ一２Ａ型片段和ＥＢＮＡ表达检测中任一项阳性作为ＥＢ病毒感染、整合或表达的依据，则鼻咽癌组与非癌组之间有明显的差别（Ｐ＜０．００１）。这从另一角度提示ＥＢ病毒（特别是ＥＢＮＡ一２Ａ型）感染与我区鼻咽癌病因、发病有密切关系。     

EB病毒核抗原1对鼻咽癌细胞miR-34a/Notch1轴及增殖、凋亡的影响

目的:探讨EB病毒核抗原1（Epstein-Barr virus nuclear antigen1,EBNA1）对鼻咽癌细胞miR-34a/Notch1轴及增殖、凋亡的影响。方法:体外培养人EB病毒（Epstein-Barr virus,EBV）阴性和阳性鼻咽癌细胞系CNE2、C666-1,CNE2细胞设置对照组、空转...     

EB病毒gp85 N端片段的原核表达与初步鉴定

目的：构建EB病毒基因的原核表达载体，并在大肠杆菌中进行表达。分析非糖基化的EB病毒包膜糖蛋白gp85N端截短片段的抗原性。方法：采用基因工程技术，以B95—8细胞（美洲绒猴外周血B淋巴细胞经EBV转化后的细胞系）培养上清为模板，用PCR扩增EB病毒的BXLF2基因N端片段。PCR产物经Hind Ⅲ和XhoⅠ双酶切，插入原核表达载体pGEX-5T中，构建pGEX5T-85N重组表达质粒，并在大肠杆菌BL21中诱导表达gp85N蛋白。纯化表达的蛋白用Westernblot鉴定，并免疫BALB／c小鼠。结果：序列分析表明，插入片段的序列与GenBank登录的参考序列完全一致。重组表达的蛋白的相对分子质量（Mr）约为45000，同预期的大小相符。以纯化的可溶性重组蛋白免疫BALB／c小鼠，经ELISA检测获得了高效价的抗血清，且抗gp85单克隆抗体（mAb）可识别所表达的gp85N抗原。Westernblot显示，该抗原可与小鼠免疫血清起特异性反应。结论：表达并纯化的EB病毒截短的gp85N重组蛋白具有良好的抗原性，为下一步分析所产生抗体的生物学特性提供了条件。     

EB病毒编码的信号转导模拟分子研究进展

EB病毒 (EBV)与人类的伯基特淋巴瘤、霍杰金氏淋巴瘤、鼻咽癌密切相关 ,现在越来越多的肿瘤中发现有该病毒。在EBV编码的多种蛋白中 ,有些蛋白分子从结构或功能上模拟、利用了细胞内外的信号转导分子从而干扰了细胞正常的信号转导 ,导致EBV感染组织或细胞出现多种异常的生物学效应。     

肺癌组织中EB病毒感染的检测

目的探讨原发性肺癌中EB病毒（Epstein—Barr virus，EBV）的存在情况及EBV与原发性肺癌的关系。方法唐山市人民医院和开滦医院病理科储存的2001--2006年肺癌手术切除石蜡包埋肺癌组织108份，癌旁组织22份，以EBV阳性鼻咽癌组织为阳性对照，用原位杂交法（ISH）检测肺癌患者石蜡包埋组织标本中EBV编码的小RNA（EBERl），并采用图像分析法进行形态学定量。结果癌组织及癌旁组织EBERl的阳性率分别为33．3％（36／108）和4．5％（1／22），二者间差异有统计学意义（P〈0．01）。鳞癌、腺癌、小细胞癌及大细胞癌中EBV感染率分别是35．9％（14／39）、31．6％（12／38）、31．0％（9／29）和1／2。EBV感染与患者年龄、性别和组织学类型无关，但与肺癌的部位、癌组织分化程度有关，右肺明显高于左肺，中低分化癌明显高于高中分化癌。结论唐山地区原发性肺癌组织中EBV感染率为33．3％，EBV感染可能是肺癌的潜在病因之一，在癌组织分化的不同阶段有不同的作用。     

Epstein-Barr virus DNA in nasopharyngeal biopsies

The Epstein-Barr virus (EBV) has been closely associated with the undifferentiated form of nasopharyngeal carcinoma (NPC), which is particularly common in the high risk area in southeast China. We have examined 37 nasopharyngeal biopsies from patients within this high risk area, including 31 cases of undifferentiated NPC and 6 cases of patients with nasopharyngitis, for the presence of EBV DNA. We found that 26 of 31 biopsies from NPC patients were EBV DNA positive; 3 of the 6 biopsies from patients diagnosed with nasopharyngitis were also EBV DNA positive. Southern blot analysis of the DNAs obtained from the EBV genome positive biopsies, digested with EcoRI, showed that all preparations from the NPC tumors had only one band corresponding to the EcoRI A fragment when a BamHI W fragment was used as a probe. However, one tumor had an additional band with a molecular weight larger than EcoRI A. The presence of this novel band could indicate the integration of viral DNA into host cellular DNA. DNA from the same biopsies were restricted with BamHI and PstI restriction enzymes. The data obtained from these experiments suggest that the EBV genomes in both the NPC tumor biopsies and biopsies from nasopharyngitis patients obtained from an endemic area in South China may be similar to each other and to the B95-8 EBV isolate with respect to the BamHI Y region of the EBV genome. The data also demonstrate that infection of normal nasopharyngeal epithelial cells with EBV takes place in patients with nasopharyngitis.     

Detection of EBV and HPV in nasopharyngeal carcinoma by in situ hybridization

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a common cancer in Southeast Asia and is frequently associated with Epstein-Barr virus (EBV). Human papilloma virus (HPV) is an epitheliotrophic oncogenic virus that has been detected in a variety of head and neck tumors including NPC. This retrospective study was undertaken to investigate the prevalence of EBV and HPV infection subtypes 6/11 and 16/18 in 20 patients with NPC. METHODS: In situ hybridization for EBV-encoded RNA (EBER) and tyramid signal amplification of ISH for HPV DNA subtypes 6/11 and 16/18 was performed to evaluate the prevalence of EBV and HPV latency infection among Iranian Patients with NPC. RESULTS: 16 cases were classified as WHO type III (undifferentiated carcinoma) and 4 as WHO type II (non-keratinizing SCC). EBER-ISH was positive in 19 (95%) of NPCs evaluated and in one metastases from cervical primary, included in this series. Two of 20 NPC (10%) contained HPV 6/11 sequences and two of 20 NPC (10%) contained HPV 16/18 sequences, and combined EBV and HPV infection was detected in 3 of the 20 (15%) patients. CONCLUSION: Our data indicated that EBV is closely associated with NPC in Iran. In addition, a low percentage of EBV positive NPC contained HPV sequences. The significance of coexistence of EBV and HPV in NPC requires further study.     

Prevalence and relevance of EBV latency in nasopharyngeal carcinoma in Israel

BACKGROUND: Nasopharyngeal carcinoma (NPC) is frequently associated with Epstein-Barr virus (EBV). The incidence of NPC in Western countries is lower than in the Far East, and EBV latency in NPC is less prevalent. Israel, as a part of the Mediterranean area, is one of the countries with an intermediate risk for NPC. METHODS: Immunohistochemistry (IHC) for latent membrane protein 1 (LMP-1) and in situ hybridisation (ISH) for EBV encoded RNA (EBER) were used to evaluate the prevalence and possible prognostic value of EBV latency among Israeli patients with NPC. Forty five patients with different NPC histologies were studied. RESULTS: LMP-1 IHC was positive in six samples only, all with undifferentiated histology. EBER ISH was positive in 40 of the 45 samples. According to histological type, three of five patients with squamous cell carcinoma were EBV positive and 37 of 40 non-keratinising and undifferentiated carcinoma cases were positive. Although EBV was more prevalent in patients with non-squamous carcinoma, the difference was not significant, probably because of the small number of patients with keratinising carcinoma. With regard to the clinical categories and survival, no significant difference could be detected between patients who were positive or negative for EBER ISH. No association was found between EBV latency and patient sex, age, origin, stage, or survival. CONCLUSIONS: NPC in Israel is highly associated with EBV latency as detected by EBER ISH. LMP-1 IHC is considerably less sensitive in detecting EBV latency in NPC among the same patient group.     

Expression of Epstein–Barr-virus-encoded small nuclear RNA in nasopharyngeal carcinomas of Aegean Turkish patients

Nasopharyngeal carcinomas (NPC) are epithelial neoplasms which show a distinct geographical distribution and have a characteristic histology. These tumors have multifactorial etiology, including virological, environmental, and genetic components. The aim of the present study is to assess the relation between Epstein–Barr-virus (EBV) and subtypes of NPC in Aegean Turkish patients. In the present study, nasopharyngeal biopsies of 84 cases diagnosed as nasopharyngeal carcinoma, between 1998 and 2004, were reevaluated. In situ hybridization with the fluorescein-conjugated EBV-encoded small nuclear RNA (EBER) oligonucleotide probe was performed on paraffin-embedded tissue sections using an automated slide stainer system. Of 84 patients, 55 were men and 29 were women with ages ranging between 7 and 77 years (median 50, mean 46.73). Seventy-three of 84 cases were EBER positive. All of 62 cases (100.0%) with undifferentiated carcinoma, 8 of 16 (50.0%) with differentiated nonkeratinizing carcinoma, and three of six (50.0%) with keratinizing squamous cell carcinoma were EBV positive. EBER positivity was statistically significantly higher in undifferentiated carcinomas, compared to the other morphological subtypes (p = 0.000). Our results showed that all morphological subtypes of NPC are highly associated with EBV latent infection in our region, and a higher prevalence was found for the undifferentiated subtype.     

Distribution of Epstein-Barr virus genotypes in throat washings, sera, peripheral blood lymphocytes and in EBV positive tumor biopsies from Slovenian patients with nasopharyngeal carcinoma

Nasopharyngeal carcinoma (NPC) is a malignancy closely associated with Epstein-Barr virus (EBV). It is prevalent among the Chinese of Southern China, whereas outside China, the position seems to be different. The aim of this study was to determine the distribution of EBV genotypes in the patients with NPC in Slovenia, which is a nonendemic area. Detection of EBV was undertaken by testing the throat washes, sera, peripheral blood lymphocytes (PBLs), and biopsies of primary tumors of 48 patients with NPC in Slovenia. The sera of 20 patients with serologically confirmed primary EBV infection served as a control clinical material. The analysis of genotypes was carried out on three regions of EBV genome; BamHI WYH, BamHI I, and BamHI F, using the polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). The results show that, in Slovenia, the predominant combination of EBV genotypes based on the differences in the three genomic regions is ADF. This combination was found in 56 out of 103 different EBV positive clinical samples (throat washes, sera, PBLs, and tumor biopsies) of patients with NPC and in 15 out of 17 sera of patients with primary EBV infection. Very low number of genotypes C and f were detected, in spite of the fact that these two genotypes were considered to be associated with the development and/or maintenance of NPC in Southern China. Genotype f was found in only two tumor biopsies; in all other clinical samples (throat washes, sera and PBLs), genotype F was detected. Genotype C was proven in 31/103 clinical samples, with the highest percentage in tumor biopsies (37.5%). As in the NPC patients from other countries (Alaska is an exception), genotype A was predominant and was detected in 86/103 clinical samples. Genotype B was found in 15 clinical samples of patients with NPC and in 3 the two genotypes A and B were found. In comparison to China, these results show different EBV genotypes distribution. It seems that the genetic disposition of human population is an important factor that may contribute to different susceptibility for specific EBV genotypes.     

Detection of Epstein-Barr Virus DNA in well and pooly differentiated nasopharyngeal carcinoma cell lines

Undifferentiated and poorly differentiated nasopharyngeal carcinoma (NPC) were know to be tightly associated with Epstein-Barr Virus (EBV). Its association with well differentiated NPC was also reported. In the present study, the presence of EBV was investigated by nucleic acid hybridization, Polymerase Chain Reaction (PCR), Immunoblot andin situ hybridization in two well differentiated NPC cell lines (CNE-1 and HK-1) and two other poorly differentiated NPC cell line (CNE-2 and CNE-3). Contrary to previous report indicating the absence of EBV in these cell lines, EBV DNA and proteins were present in all cell lines. The detection of EBV became more easily when the investigation was carried out on the nude mice tumor induced by transplantation of each NPC epithelial cell line. The EBV latent membrane protein (LMP1) was found byin situ hybridization to be intergrated partly in the chromosomal DNA of these cell lines. The observations indicate that EBV could persist for a long time in the carcinoma cells established directly from well and poorly differentiated tumor biopsies and from transplantable NPC tumor in nude mice.     

A20 RNA expression is associated with undifferentiated nasopharyngeal carcinoma and poorly differentiated head and neck squamous cell carcinoma

A20 is an anti-apoptotic gene that can be induced in human epithelial cell lines in response to expression of the Epstein–Barr virus (EBV) gene product latent membrane protein 1 (LMP1). EBV is a ubiquitous, persistent human herpesvirus that is consistently associated with undifferentiated nasopharyngeal carcinoma (NPC), in which antigen expression includes LMP1. Consistent with a potential role in the development of NPC, LMP1 has profound effects on epithelial cell growth. A20 may be a key downstream effector of LMP1 in NPC, as LMP1-induced A20 blocks p53-mediated apoptosis in H1299 epithelial cells and most NPCs have wild-type p53. Moreover, the potential role of A20 in the development of epithelial malignancies may extend to tumours not associated with EBV. The purpose of this study was to develop an in situ hybridization assay to assess expression of A20 RNA in undifferentiated NPC and in non-EBV-associated poorly differentiated head and neck squamous cell carcinomas (SCCs) and well-differentiated SCCs of the skin. A20 RNA expression was also examined in normal samples of oral mucosa and skin. Expression of A20 was demonstrated in 76 per cent of undifferentiated NPCs and in 80 per cent of poorly differentiated head and neck SCCs, suggesting a role for A20 in the pathogenesis of these epithelial malignancies. By contrast, A20 RNA was not detected in well-differentiated SCCs of the skin, or in any normal samples of squamous epithelial tissue. The pathway leading to A20 expression in non-EBV-associated poorly differentiated head and neck SCCs is clearly LMP1-independent. LMP1 expression was demonstrated in 29 per cent of NPC biopsies, suggesting an LMP1-independent pathway to A20 induction in undifferentiated NPC. Copyright © 1999 John Wiley & Sons, Ltd.     

Comparative analysis of the expression of the Epstein-Barr virus (EBV) anti-apoptotic gene BHRF1 in nasopharyngeal carcinoma and EBV-related lymphoid diseases

Epstein-Barr virus (EBV) has been identified in a wide range of neoplastic and non-neoplastic disorders. The EBV open reading frame BHRF1 encodes a protein with partial sequence and functional homology to the anti-apoptotic onco-protein Bcl-2 and may therefore have a role in the proliferation of EBV positive cells. We have developed a rat monoclonal antibody against pBHRF1, which can detect BHRF1 in paraffin sections. While a number of mutant versions of BHRF1 were recognised, the monoclonal did not detect the BHRF1 homologue encoded by Herpesvirus papio or two mutants with deletions in the BH2 region. This novel rat monoclonal antibody (6A9) was used to examine tissue sections from 39 cases of non-keratinising undifferentiated nasopharyngeal carcinoma (NPC), 6 cases of metastatic NPC, 7 cases of EBV-positive NPC with squamous differentiation from Chinese patients, 15 cases of EBV-positive post-transplant lymphoproliferative disorder (PTLD), 6 EBV-containing lymphoblastoid cell lines, and 2 cases of oral hairy leukoplakia (OHL). In 11 cases of undifferentiated NPC, RT-PCR data were available for comparison with the immunohistochemistry. Both cases of OHL and two cases of LCL were positive for BHRF1 but none of the PTLD showed positive staining. All cases of undifferentiated NPC were positive for Bcl-2 but only one BHRF1 positive cell was identified in 1 of 39 cases of primary undifferentiated NPC. The 6A9 antibody produced less background staining and no nuclear positivity compared with the commercially available mouse monoclonal 5B11. It is concluded that BHRF1 can not be detected by immunohistochemistry in NPC and therefore it appears not to play a significant anti-apoptotic role in the progression of this EBV-associated tumour. The 6A9 monoclonal appears to be superior to 5B11 for the detection of pBHRF1 in tissue sections.     

Detection of latent Epstein-Barr virus (EBV) DNA in paraffin sections of nasopharyngeal carcinomas expressing no EBV-encoded small RNAs using in situ PCR

Summary.  In situ hybridization (ISH) with EBER 1 (Epstein-Barrvirus (EBV)-encoded small RNA1) probes is widely used for in situ detection of EBV-infected cells. ISH with an EBER1 probe showed that 10 of 40 NPC cases were negative for EBER1 expression. For in situ detection of EBV DNA, we used in situ PCR method which can detect one copy of EBV DNA per cell. Of the 10 EBER1-negative cases, three cases including one each of well- and poorly differentiated carcinomas and undifferentiated carcinoma were EBV DNA-positive by in situ PCR. The remaining seven were truly negative for the presence of EBV DNA. All the EBV genome-negative NPC cases examined here were histologically classified as poorly differentiated or undifferentiated carcinomas which are known to be closely associated with EBV, indicating the existence of EBV DNA-negative NPC cases, regardless of histological type or differentiation. These results indicate that there are EBV genome-positive NPC cases expressing no EBER1 and that in situ PCR can be suitable for in situ detection of EBV-infected cells, especially those expressing no EBER1 in paraffin sections. Received April 14, 1997 Accepted June 5, 1997     

Detection of EBV in nasopharyngeal carcinoma by quantum dot fluorescent in situ hybridization

Aims

Nasopharyngeal carcinoma (NPC) is a common cancer in Southeast Asia and is frequently associated with Epstein–Barr virus (EBV) infection. The primary aim of this study was to improve the method of EBV detection by exploring quantum dots in FISH detection, and compare QD-based FISH with conventional ISH.

Materials and methods

Biopsy specimens were retrospectively retrieved from 35 NPC patients as paraffin-embedded tissue blocks. QD-FISH was developed to detect the presence of EBV encoded small RNA (EBER) using biotin-labeled EBER oligonucleotide probe indirectly labeled with streptavidin-conjugated quantum dots. Conventional ISH was also performed using a commercial kit to assess concordance between the two methods.

Results

All the 35 NPC cases were nonkeratinizing carcinoma (7 differentiated and 28 undifferentiated subtypes). EBER-positive signals were detected in 91.43% (32/35) and 80% (28/35) cases by QD-FISH and ISH, respectively. There was no significant difference in the number of EBER-positive cases by the two methods. A moderate concordance was found between QD-FISH and ISH for EBER status (κ = 0.55). Four EBER-negative cases by ISH showed EBER-positive signals when detected by QD-FISH.

Conclusions

EBV is closely associated with NPC in Chinese patients. QD-FISH is a novel effective method for EBER detection, and has a moderate concordance with conventional ISH.