Epstein-Barr virus infection and persistence in nasopharyngeal epithelial cells

Epstein-Barr virus（EBV） infection is closely associated with undifferentiated nasopharyngeal carcinoma（NPC）, strongly implicating a role for EBV in NPC pathogenesis; conversely, EBV infection is rarely detected in normal nasopharyngeal epithelial tissues. In general, EBV does not show a strong tropism for infecting human epithelial cells, and EBV infection in oropharyngeal epithelial cells is believed to be lytic in nature. To establish life-long infection in humans, EBV has evolved efficient strategies to infect B cells and hijack their cellular machinery for latent infection. Lytic EBV infection in oropharyngeal epithelial cells, though an infrequent event, is believed to be a major source of infectious EBV particles for salivary transmission. The biological events associated with nasopharyngeal epithelial cells are only beginning to be understood with the advancement of EBV infection methods and the availability of nasopharyngeal epithelial cell models for EBV infection studies. EBV infection in human epithelial cells is a highly inefficient process compared to that in B cells, which express the complement receptor type 2（CR2） to mediate EBV infection. Although receptor（s） on the epithelial cell surface for EBV infection remain（s） to be identified, EBV infection in epithelial cells could be achieved via the interaction of glycoproteins on the viral envelope with surface integrins on epithelial cells, which might trigger membrane fusion to internalize EBV in cells. Normal nasopharyngeal epithelial cells are not permissive for latent EBV infection, and EBV infection in normal nasopharyngeal epithelial cells usually results in growth arrest. However, genetic alterations in premalignant nasopharyngeal epithelial cells, including p16 deletion and cyclin D1 overexpression, could override the growth inhibitory effect of EBV infection to support stable and latent EBV infection in nasopharyngeal epithelial cells. The EBV episome in NPC is clonal in nature, suggesting that NPC develops from a single     

A Follow－up Survey of 42048 Subjects Tested with Epstein－Barr Viral Serology in a High －incidence Area of Nasopharyngeal Carcinoma

Objective:To evaluate the efficiency of Epstein-Bar viral serology in detecting nasopharyngeal carcinoma(NPC)and comparing the NPC risks between serology-positive and serology-negative subjects.MethidsLUnnybiebztnatuc tutratuib for VCA-IgA was performed in 42048 subjects between the ages of 30 and 59.The titre of VCA-IgA,≥1/5,EA-IgA,≥1/5 was recognized as being positive.All those were followed up to the end of 1999.Results:45 NPCs were detected in the first year(45/42048,107.02/10^5).The average annual incidence of NPC in 3050 VCA-IgA-positive subjects(144.86/10^5)was higher than that(11.98/10^5)in 38953 VCA-IgA-negative subjects during the next 12 years.72 out the 154 NPC patients detected were of stage-I.Conclusion :This reveals that EBV serology could actually detect early-stage NPCs as previously reported.Meaningfully,the NPC risk increased 12 times the VCA-IgA-negative subjects in the VCA-IgA-positive subjects after the first-turn serological screening.The 5-year and 10-year survival rates of stage-I NPC patients(81.25%,67.39% respectively)were both significantly higher than those of the stage-II A, stage-II B and stage-Ⅲ patients (60.32%,26.67% respectively)after radiotherapy.     

ESTABLISHMENT OF A NOVEL CELL LINE (HNE_(1)) DERIVED FROM A NASOPHARYNGEAL CARCINOMA

A novel epithelial cell line, designated HNE1 was established from a biopsy specimen of a naso-pharyngeal carcinoma (NPC). Electron microscopic examination of the HNE1 cells demonstrated bi-directional differentiation, with some cells displaying features of poorly differentiated squamous cell carcinoma, while other cells appeared to have the morphology of poorly differentiated adenocarcinoma. The HNE1 cell line has been passaged more than 100 times over a period of one year. We recently reported that the Epstein-Barr virus (EBV) nuclear antigen (EBNA) was detected in a low pe rcentage of the HNE1 cells examined at subcultures 5-81; the cells were also shown to be EBV DNA positive. Tumorigenicity of the HNE1 cells was demonstrated by xentransplanta tion in athymic nude mice. The developed tumors were characterized as well-differentiated squamous cell carcinomas upon histological examination. Kar yotypic analysis of the HNE1 cells demonstrated an aneuploidy with a modal chromosomal number of 74 at passage     

Analysis of serum levels of IgA antibodies to Epstein Barr virus capsid antigens in the spouses and the children of patients with nasopharyngeal carcinoma

OBJECTIVE To analyze the serum levels of IgA antibodies to Epstein Barr virus capsid antigens （EBV/IgA/VCA） in patients with nasopharyngeal carcinoma （NPC） and in their spouses and children in order to further evaluate the risk of developing the disease in family members of NPC patients. METHODS Four categories of sera were used to detect EBV/ IgA/VCA using the immunoenzyme method. In our study 317 biopsy-confirmed NPC patients, 317 spouses and 317 children of the NPC patients, as well as 413 healthy subjects as the controls that came from the same area were enrolled. RESULTS The positive rate of EBV/lgA/VCA was 97.2%, 14.2%, 19.9% and 3.1% in the NPC patients, the spouse and child groups, and in the control group, respectively. The positive rate was significantly higher in the NPC group than in the other 3 groups, and it was also significantly higher in the spouse and in the child groups than in the control group （P 〈 0.001）. The results of the relative to identified distribution unit （Ridit） analysis showed that the average Ridit values were 0.860, 0.404, 0.424 and 0.356 respectively in the NPC patients, in the spouse and child groups, and in the control group. The antibody titer of IgA/VCA was significantly higher in the NPC group than in the other 3 groups, and it was also significantly higher in both the spouse and child groups than in the control group （P 〈 0.001）. The OR values of positive EBV/IgA/VCA antibody were 5.09 and 7.63, respectively in the spouse and child groups. No significant differences were found in the positive rates or in the titers of IgA/VCA antibody between the groups of spouses and children （P 〉 0.05）. CONCLUSION Positive detection of EBV/IgA/VCA antibody occurs in familial aggregation, as there is ample opportunity for EBV reactivation in the spouses and in the children of NPC patients. These individuals with a high risk of developing the NPC should be closely followed in order to detect the disease at an early stage.     

Carcinogenesis ofnasopharyngeal carcinoma：an alternate hypothetical mechanism

Current proposed mechanisms implicate both early and latent Epstein–Barr virus (EBV) infection in the carcinogenic cascade, whereas epidemiological studies have always associated nasopharyngeal carcinoma (NPC) with early child-hood EBV infection and with chronic ear, nose, and sinus conditions. Moreover, most patients with NPC present with IgA antibody titers to EBV capsid antigen (VCA-IgA), which can precede actual tumor presentation by several years. If early childhood EBV infection indeed constitutes a key event in NPC carcinogenesis, one would have to explain the inability to detect the virus in normal nasopharyngeal epithelium of patients at a high risk for EBV infection. It is perhaps possible that EBV resides within the salivary glands, instead of the epithelium, during latency. This claim is indirectly supported by observations that the East Asian phenotype shares the characteristics of an increased sus-ceptibility to NPC and immature salivary gland morphogenesis, the latter of which is inlfuenced by the association of salivary gland morphogenesis with an evolutionary variant of the human ectodysplasin receptor gene (EDAR), EDARV370A. Whether the immature salivary gland represents a more favorable nidus for EBV is uncertain, but in patients with infectious mononucleosis, EBV has been isolated in this anatomical organ. The presence of EBV-induced lymphoepitheliomas in the salivary glands and lungs further addresses the possibility of submucosal spread of the virus. Adding to the fact that the fossa of Rosen Müller contains a transformative zone active only in the ifrst decade of life, one might be tempted to speculate the possibility of an alternative carcinogenic cascade for NPC that is perhaps not dissimilar to the model of human papillomavirus and cervical cancer.     

Detailed Deletion Mapping of Chromosome 9p21-22 in Nasopharyngeal Carcinoma

Previous studies have showed that Epstein-Barr virus (EBV) infection, certain environmental factors and genetic factors were found to be closely associated with nasopharyngeal carcinoma. The rates of NPC in southern China and southeast Asia are 25 times higher than that of in western countries. The statistic analysis revealed 5%-10% NPC patients have family history, there, genetic susceptibility might be an important factor in the pathogenesis of NPC. Unfortunately the alterations of com…     

DYNAMIC PARAMETER OF MEMBRANE LIPID IN LUNG CANCER CELL LINES, CARCINOGENESIS CELLS AND CANCER CELLS ISOLATED FROM PATIENTS WITH LUNG CANCER

With the aid of the Fluorescent lipophilic probe DPH (1, 6- diphenyl- 1, 3, 5- hexatriene ), the degree of microviscosity (η) and lipid fluidity (LFU) obtained from lung cancer lines and carcinogenesis cells induced by irradiation as well as the patients with lung cancer were quantitatively monitored by Fluorescence polarization. The results have shown a marked decreased in η and a significant increase in LFU in various tumor cells as compared to normal cells. Sometime, the degree of fluidity in carcinogenesis cells Induced by radiation and the patients with lung cancer have shown to be similar pattern. The possibility that these dynamic parameter may serve as a diagnostic tool for an early detection of lung cancer is discussed.     

The interplay of host genetic factors and Epstein-Barr virus in the development of nasopharyngeal carcinoma

The interplay between host cell genetics and Epstein-Barr virus（EBV） infection contributes to the development of nasopharyngeal carcinoma（NPC）. Understanding the host genetic and epigenetic alterations and the influence of EBV on cell signaling and host gene regulation will aid in understanding the molecular pathogenesis of NPC and provide useful biomarkers and targets for diagnosis and therapy. In this review, we provide an update of the oncogenes and tumor suppressor genes associated with NPC, as well as genes associated with NPC risk including those involved in carcinogen detoxification and DNA repair. We also describe the importance of host genetics that govern the human leukocyte antigen（HLA） complex and immune responses, and we describe the impact of EBV infection on host cell signaling changes and epigenetic regulation of gene expression. High-power genomic sequencing approaches are needed to elucidate the genetic basis for inherited susceptibility to NPC and to identify the genes and pathways driving its molecular pathogenesis.     

Familial nasopharyngeal carcinomas possess distinguished clinical characteristics in southern China

Objective： To compare clinical characteristics between familial nasopharyngeal carcinomas（NPCs） and sporadic NPCs in Guangdong province, China, a high-risk area.
Methods： Between 1991 and 2001, 993 NPC patients treated at the Cancer Center of Sun Yat-Sen University in Guangdong were randomly selected as probands. Information about NPC among the probands＇ relatives and other information were obtained from a retrospective review of the patients＇ medical records. The patients were divided into sporadic NPC, low-frequency familial NPC（one NPC patient in addition to the proband in three generations）, and high-frequency familial NPC（2 or more additional NPC patients in three generations） groups. Pathological and clinical characteristics were compared among these groups.
Results： Of the 993 patients, 131（13.2%） had a familial history of NPC. The average age at diagnosis was the lowest in the high-frequency familial NPC group（39 years; P=0.048）. Although the overall survival（OS）, distant metastasis-free survival（DMFS）, and disease-free survival（DFS） rates did not differ between familial and sporadic NPCs, the locoregional recurrence-free survival（LRFS） rate increased in the order sporadic NPCs, low-frequency familial NPCs, and high-frequency familial NPCs（P=0.009）, with 5-year rates of 70%, 83%, and 87%, respectively. Multivariate analysis showed that family history of NPC was an independent favorable prognostic factor for LRFS, with adjusted hazard ratio（a HR） of 0.548, 95% CI（0.342-0.878）. The high LRFS for familial NPCs was mainly noted among young, advanced-stage patients who received continuous radiation treatment.
Conclusions： Genetic factors may play an important role in the etiology of high-frequency familial NPC and underlie the early age of onset and sensitivity to radiotherapy.     

Expression of mir-34c-5p and mir-150-5pin nasopharyngeal carcinoma and up-regulated expression after invasion and apoptosis of nasopharyngeal carcinoma cells

Objective MiRNAs are closely related to tumors,and we hypothesized there is specific miR expression in nasopharyngeal carcinoma(NPC).We intended to investigate the expression of mir-34c-5p and mir-150-5p in NPC and to investigate the effects of mir-34c-5p and mir-150-5p on apoptosis and invasion following up-regulated expression in HNE1 NPC cells.Methods MiR-34c-5p and miR-150-5p expression levels in 30 individual cases of NPC and nasopharyngitis were detected with gene chip and qRT-PCR techniques.miR-34c-5p and miR-150-5p were transfected into the NPC cell line HNE1 via liposomes.Their expression levels were detected with qRT-PCR,apoptosis was evaluated by flow cytometry,and invasion ability was assessed via Transwell migration assay.Results MiR-150-5p expression levels in NPC and nasopharyngitis were 0.165±0.092 and 1.062±0.280 respectively,and miR-34c-5p expression levels in NPC and nasopharyngitis were 0.417±0.220 and 1.385±0.739,respectively,which indicated miR-34c-5p and miR-150-5p were weakly expressed in NPC.Apoptosis rates in HNE1 cells transfected by miR-34c-5p and miR-150-5p were increased,by 12.7%and 7.6%,respectively,which were significantly higher compared to blank control(3.9%).The Transwell assay demonstrated that invasive HNE1 cell counts were 32.00±2.00 and 28.33±2.08,respectively,compared to 60.66±8.50 in the blank control(P<0.001).Conclusion MiR-34c-5p and miR-150-5p are lowly expressed in NPC,and their down-regulation may be associated with NPC.     

鼻咽癌细胞EB病毒早期抗原（EA—R）的表达：采用单克隆抗体BAE—5的观察

以正丁酸和巴豆油诱导的Raji细胞为免疫原,应用杂交瘤技术制备一种抗EB病毒(EBV)早期R型抗原(EA-R)的鼠IgM单克隆抗体,命名为BAE-5。以BAE-5为一抗应用APAAP免疫组织化学技术检测34例鼻咽癌和29例非鼻咽癌,结果表明,所有的鼻咽癌(34例)和29例非鼻咽癌肿瘤中的9例能与BAE-5显阳性反应。与已进行EB病毒DNA原位杂交的34例鼻咽癌结果对比认为:大多数鼻咽癌细胞不仅可检测出EBV-DNA,而且这些细胞中的一部分还可表达EA-R。说明这些细胞中的EBV-DNA处于激活状态。一些非鼻咽癌肿瘤能与BAE-5起阳性反应,可能是由于这些肿瘤细胞中也有EB病毒早期抗原存在或者可能存在与EA-R抗原决定簇相类似结构的多肽而引起交叉反应。作者认为这些结果对了解EB病毒有关的多肽,特别是EA复合物在鼻咽癌和一些含EBV-DNA的非鼻咽癌肿瘤的发生和发展中的作用具有理论意义。     

Noninvasive diagnosis of nasopharyngeal carcinoma: nasopharyngeal brushings reveal high Epstein-Barr virus DNA load and carcinoma-specific viral BARF1 mRNA

Nasopharyngeal carcinoma (NPC) is the most prevalent ENT-tumour in Indonesia. We investigated the primary diagnostic value of Epstein-Barr virus (EBV) DNA load and mRNA detection in noninvasive nasopharyngeal (NP) brushings, obtained prospectively from consecutive Indonesian ENT-patients with suspected NPC (N=106) and controls. A subsequent routine NP biopsy was taken for pathological examination and EBER-RISH, yielding 85 confirmed NPC and 21 non-NPC tumour patients. EBV DNA and human DNA load were quantified by real-time PCR. NP brushings from NPC patients contained extremely high EBV DNA loads compared to the 88 non-NPC controls (p<0.0001). Using mean EBV DNA load in controls plus 3 SD as cut-off value, specificity, sensitivity, positive and negative predictive values were 98, 90, 97 and 91%, respectively. Epstein-Barr nuclear antigen 1 (EBNA1) and the carcinoma-specific BARF1 mRNA were detected by nucleic acid sequence based amplification and found in 86 and 74% of NP brushings, confirming NPC tumour cell presence. EBV RNA positivity was even higher in fresh samples stored at -80 degrees C until RNA expression analyses (88% for both EBNA1 and BARF1). EBV RNA-negative NP brushings from proven NPC cases had the lowest EBV DNA loads, indicating erroneous sampling. No EBV mRNA was detected in NP brushings from healthy donors and non-NPC patients. In conclusion, EBV DNA load measurement combined with detection of BARF1 mRNA in simple NP brushings allows noninvasive NPC diagnosis. It reflects carcinoma-specific EBV involvement at the anatomical site of tumour development and reduces the need for invasive biopsies. This procedure may be useful for confirmatory diagnosis in large serological NPC screening programs and has potential as prognostic tool.     

Laboratory markers of tumor burden in nasopharyngeal carcinoma: a comparison of viral load and serologic tests for Epstein-Barr virus

Epstein-Barr virus (EBV) is present within the tumor cells of most cases of nasopharyngeal carcinoma (NPC). Recent studies suggest that tumor burden is proportional to the level of EBV DNA in blood and that rapid blood testing can be used to guide therapeutic intervention. The relative utility of viral load vs. serology has been insufficiently studied. In our study, EBV viral load was measured by quantitative PCR using either real-time or end-point detection systems in serum samples from 124 NPC patients (93 pretreatment, 13 relapsed, 18 in remission) and 40 controls. Serologic titers against EBV early antigen were measured in the same serum samples. EBV DNA was detectable in 64 of 93 untreated NPC patients (69%; mean viral load 11,211 copies/ml), 11 of 13 relapsed NPC patients (85%; mean 53,039 copies/ml) and 0 of 18 remission patients. EBV DNA was detectable in only 1 of 40 non-NPC controls (3%). In 34 instances where paired plasma and serum samples were available for testing, both were effective sample types, and there was no significant difference between end-point and real-time methods for measuring viral load. Early antigen (EA) IgA and IgG titers were elevated in most NPC patients regardless of whether their disease was active or in remission. EBV viral load was more informative than was EA serology for distinguishing remission from relapsed disease. EBV DNA measurement appears to be a noninvasive way to monitor tumor burden after therapy.     

Expression of Epstein-Barr virus-encoded proteins in nasopharyngeal carcinoma

Expression of the Epstein-Barr virus (EBV) encoded nuclear antigens (EBNA 1 to 6) and membrane-associated protein (LMP) was investigated by immunoblotting in 83 nasopharyngeal carcinoma (NPC) biopsies and 25 other tumor and normal tissue specimens from the head and neck region. Fifty-eight of the 83 NPC biopsies were large enough to yield parallel data on virus DNA and viral expression. All 16 cases of clinically diagnosed and histologically confirmed NPCs from North Africa contained EBV DNA and expressed EBNA-1. Of 31 clinically diagnosed NPCs from China, 29 contained EBV DNA and 25 of these expressed EBNA-1. One control tissue biopsy from the oropharynx of NPC patients contained EBV DNA, but none expressed EBNA-1. The latent membrane protein (LMP) was detected in 22/31 of the Chinese and in 10/16 of the North African NPC biopsies. None of the NPC biopsies or control tissues expressed detectable amounts of EBNA 2 or any of the other 4 nuclear antigens which are invariably expressed in EBV-transformed B cells. A smaller number of tumors from Malaysia and East Africa exhibited a similar pattern of expression. EBV was rescued from a nude-mouse-passaged North African NPC tumor by co-cultivation of the tumor cells with umbilical cord blood lymphocytes. The tumor expressed EBNA 1 and LMP, but not EBNA 2 or the other 4 EBNAs. The resulting LCLs expressed all 6 nuclear antigens, EBNA 1 to 6 and LMP. Our data suggest that expression of the EBV genome is regulated in a tissue-specific fashion.     

Frequency of Epstein Barr Virus Type 1 Among Nasopharyngeal Carcinomas in Iranian Patients

Background: Around 95% of the world’s population are infected with the Epstein-Barr virus (EBV), which can persist latent in B lymphocytes and epithelial cells life-long. EBV has been linked with lymphoid and epithelial cancers and persistence of EBV infection in lymphoid or epithelial cells may result in virus-associated B-cell tumors or nasopharyngeal carcinomas (NPC). This study was conducted to determine the frequency of EBV DNA in nasopharyngeal carcinoma tissue of Iranian patients. Materials and methods: A total of 50 blocks of formalin-fixed paraffin-embedded tissue of NPCs from 38 (76 %) male and 12 (24%) female patients were collected from archives of Ahvaz hospitals. Sections were cut at 5 μm and DNA was extracted for detection of EBV DNA and EBV typing by mested PCR. DNA sequencing was performed to confirm PCR results. The distribution of EBV DNA was compared among WHO histological subtypes of NPC. Results: Some 3 female and 11 (22%) male NPC samples showed positive for EBV DNA type 1, 2/14(22.2%)WHO histological type II and 12/41(29.3%) WHO histological type III. Conclusions: The frequency of EBV DNA among NPCs in Iranian patients was found to be 28%, EBV type I predominating. Both WHO histological type II and III NPC subtypes demonstrated approximately the same detection prevalence.     

The 30-bp deletion variant: a polymorphism of latent membrane protein 1 prevalent in endemic and non-endemic areas of nasopharyngeal carcinomas in China.

Development of nasopharyngeal carcinoma (NPC) is closely associated with Epstein-Barr virus (EBV) infection. However, NPC occurs with a marked geographic and racial distribution, whereas EBV infection is ubiquitous in the world. This leads to a question whether certain subtypes of EBV have a greater potential to induce cell transformation. Latent membrane protein 1 (LMP1) is an EBV-encoded oncogenic protein and its 30-bp deleted variant (del-LMP1) has been reported to be predominant in biopsies of NPC. We have assessed the polymorphism of LMP1 in 47 biopsies of NPC, 107 cases of throat washings (TWs) from NPC patients, and 106 cases of TWs from non-NPC patients in Guangzhou, an endemic area of NPC in southern China, as well as 103 cases of TWs from healthy donors in Haerbin, a non-endemic area of NPC in northern China. Our results found a similar extent of the LMP1 polymorphism between NPC patients and non-NPC patients in Guangzhou, with the del-LMP1 being predominant in both Guangzhou and Haerbin. Sequence analyses showed identical substitutions in other coding regions of the del-LMP1 isolated from Guangzhou and Haerbin. These results indicate that del-LMP1 represents a geographic or race-associated polymorphism rather than an NPC disease phenotype-associated polymorphism.     

Elevated expression of ICAM1 (CD54) and minimal expression of LFA3 (CD58) in Epstein-Barr-virus-positive nasopharyngeal carcinoma cells.

Undifferentiated nasopharyngeal carcinoma (NPC) is a remarkable entity among human tumors because of its constant association with the Epstein-Barr virus (EBV). Malignant epithelial cells harbor the EBV genome and often express at least 2 species of latent EBV protein (EBNA1 and LMP1). Despite the massive presence of tumor-infiltrating lymphocytes, NPC cells obviously escape immune surveillance directed to EBV antigens. Previous investigations carried out on EBV-positive Burkitt lymphoma (BL) cells have shown that this fact may be partially accounted for by a lack of expression of ICAM1 (CD54) and LFA3 (CD58). ICAM1 and LFA3 have therefore been investigated in fresh NPC biopsies and transplanted NPCs. With only 1 exception out of 9 cases, NPC cells appear to express high levels of ICAM1 and low levels of LFA3. This is a complete inversion of the pattern observed in normal epithelial cells in vivo. Additional investigations will be required to determine to what extent these characteristics affect T-cell interactions with NPC cells, specially in the process of EBV-antigen recognition.     

Quantitative detection of Epstein-Barr virus DNA methylation in the diagnosis of nasopharyngeal carcinoma by blind brush sampling

Detecting EBV DNA load in nasopharyngeal (NP) brushing samples for the diagnosis of nasopharyngeal carcinoma (NPC) has attracted widespread attentions. Currently, NP brush sampling mostly relies on endoscopic guidance, and there are few reports on diagnostic markers suitable for nonguided conditions (blind brush sampling), which is of great significance for extending its application. One hundred seventy nasopharyngeal brushing samples were taken from 98 NPC patients and 72 non-NPC controls under the guidance of endoscope, and 305 blind brushing samples were taken without endoscopic guidance from 164 NPC patients and 141 non-NPC controls (divided into discovery and validation sets). Among these, 38 cases of NPC underwent both endoscopy-guided NP brushing and blind brushing. EBV DNA load targeting BamHI-W region and EBV DNA methylation targeting 11029 bp CpG site located at Cp-promoter region were detected by quantitative polymerase chain reaction (q-PCR). EBV DNA load showed good classification accuracy for NPC in endoscopy-guided brushing samples (AUC = 0.984). However, in blind bushing samples, the diagnostic performance was greatly reduced (AUC = 0.865). Unlike EBV DNA load, the accuracy of EBV DNA methylation was less affected by brush sampling methods, whether in endoscopy-guided brushing (AUC = 0.923) or blind brushing (AUC = 0.928 in discovery set and AUC = 0.902 in validation set). Importantly, EBV DNA methylation achieved a better diagnostic accuracy than EBV DNA load in blind brushing samples. Overall, detection of EBV DNA methylation with blind brush sampling shows great potential in the diagnosis of NPC and may facilitate its use in nonclinical screening of NPC.     

鼻咽癌病人外周血和骨髓中的EB病毒与预后的临床相关性

目的通过检测NPC病人治疗前外周血和骨髓中EBV,研究EBV与NPC放疗后失败及远期生存的临床相关性.方法1998年2月至同年8月,选择诊断明确的27例晚期NPC病人,其中24例为初治、3例为局部复发,疗前用常规PCR分别检测外周静脉血和骨髓中EB病毒.同时检测13例非NPC肿瘤病人静脉血中的EBV,作为对比.结果13例非NPC病人静脉血中EB病毒均为阴性.27例NPC中,15例EBV阳性(外周血和骨髓中EBV均阳性者13例),阳性病例中有10例治疗失败,失败率66.7%,其中6例为远处转移,远处转移率40.0%.12例阴性病人,3例疗后失败,失败率25.0%:其中仅1例为远处转移,远处转移率8.3%.两组间失败率差异明显.结论部分NPC病人外周血和骨髓中疗前即存在着EB病毒.EBV阳性组放疗后失败的发生率明显高于EBV阴性组,而且外周血与骨髓EBV有很好的相关性,提示外周血EBV的检测在临床上具有判定预后的应用价值.     

Serologic diagnosis of nasopharyngeal carcinoma. A double-blind study of four EB virus antibodies with evaluation by sequential discrimination

It is generally known that a close relationship exists between Epstein-Barr Virus (EBV) and nasopharyngeal carcinoma (NPC). Recently, patients with early lesions of NPC have been detected in the general population by use of serologic mass survey. Using the double-blind method, we have studied the diagnostic value of the four EBV antibody titers, VCA-IgA, VCA-IgG, EA-IgA and EA-IgG, in four groups of subjects, each consisting of 50 persons: patients with nasopharyngeal carcinoma (NPC group), patients with cancers other than NPC in the head and neck regions (HNC group), patients with cancers outside of head and neck regions (OC group) and normal individuals (NS group). The results of these four antibodies were evaluated both singularly and together by multivariate sequential discrimination. Taking 1:10 as the criterion of being positive, in the NPC group, the positive rate of VCA-IgA is 88%, the VCA-IgG rate is 100%, the EA-IgA rate is 48% and the EA-IgG rate is 74%. In the non-NPC group, the positive rates of VCA-IgA are as high as 86%-92%, but those of the other antibodies are as low as 0-42%. The positive rates and the geometric mean titers of these four antibodies were all elevated as compared with those in the three non-NPC groups. These differences are statistically significant. VCA-IgG is unimportant in the diagnosis of NPC because of its low specificity. By treating the antibody titers of VCA-IgA, VCA-IgG, EA-IgA and EA-IgG with sequential discrimination, the correlation rate between the serology and pathology of NPC is 88% and the false positive rate is 7.3%.