Distribution and phenotype of Epstein-Barr virus-infected cells in human pharyngeal tonsils.

Although Epstein-Barr virus (EBV) is often found in human tonsils, it remains to be precisely determined in what cells and microenvironment the virus is present. Although generally regarded as a B lymphotropic virus, EBV is associated with non-B-cell tumors, for example, NK/T-cell lymphoma, carcinoma, and leiomyosarcoma. To provide a basis for understanding the origin and biology of EBV-infected non-B cells, the immunophenotype of all EBV-infected cells in reactive human tonsils was determined by subjecting tonsil sections to dual/triple EBER in situ hybridization and immunohistochemistry with monoclonal antibodies to T cells (CD3, CD4, CD8, CCR3), B cells (CD20), plasma cells (CD138), natural killer (NK) cells (PEN5), and epithelial cells (cytokeratin), as well as frozen section immunostaining with antibodies to EBV latent proteins EBNA1, EBNA2, LMP1, and EBV early protein BZLF1. Most tonsils contained nearly equal numbers of EBNA1- and LMP1-positive cells (latency program) while only a few contained EBNA2-positive cells (growth program). More than 1000 EBER-positive cells from six tonsils were detected in the interfollicular zone (59%), tonsillar crypts (26%), and follicles (15%). Most (82%) EBER-positive cells are CD20-positive B cells, 7% are CD3-positive T cells, and 11% are cells of indeterminate lineage, often with plasmacytoid morphology. However, no EBER-positive plasma cells were identified. Rare EBER-positive NK cells and EBER/BZLF1-positive epithelial cells were identified. The direct demonstration of EBV within rare T cells, NK cells, and epithelial cells in reactive human tonsils provide a basis for further understanding of the origin of EBV-associated tumors of non-B-cell type.     

Evidence for lytic infection by Epstein-Barr virus in mucosal lymphocytes instead of nasopharyngeal epithelial cells in normal individuals.

Normal nasopharyngeal tissues from 23 individuals who died of causes unrelated to the upper respiratory system and had no evidence of Epstein-Barr virus (EBV)-related diseases were studied using in situ hybridisation (ISH) and immunohistochemistry for the detection of EBV RNA and expression of EBV proteins, respectively. ISH using ³⁵S-labelled riboprobe for EBV EBER RNA showed occasional to a few EBER + lymphocytes in the stroma of nasopharyngeal mucosa in 14/16 cases with available paraffin-embedded tissues. In addition, very rare intraep-ithelial EBER+ lymphocytes were also detected in 3/16 cases. However, in none of these cases was EBER detected in the epithelial cells. Similar results were obtained using a nonradioactive ISH method for EBER (Dako). In 3/23 cases, im-munostaining using monoclonal antibodies for EBV proteins on cryostat sections showed occasional cells in the stroma expressing EBV nuclear antigen 2 (EBNA2), latent membrane protein-1 (LMP), and switch protein encoded by BZLF1 gene (ZEBRA) in two cases and only very rare LMP+ and ZEBRA+ cells in one other case. Double immuno-staining combining alkaline phosphatase anti-alkaline phosphatase (APAAP) for CD markers and indirect immunofluorescence for LMP showed that the LMP+ cells were either CD19+ or less frequently CD3+, but none were CD68+. These results show that both B and T lymphocytes harbouring EBV can be found in the normal nasopharyngeal tissues. Interestingly, EBV proteins associated with lytic viral replication—diffuse early antigen (EA-D), viral capsid antigen (VCA), or membrane antigen (MA)—were also detected in rare cells in the stroma in one case, and in another case only one MA+ cell was detected. These results provide evidence for a lytic type of infection by EBV in the normal nasopharynx involving a very small proportion of stromal lymphocytes and support the view that nasopharyngeal lymphocytes can act as a reservoir for EBV in normal individuals. © 1995 Wiley-Liss, Inc.     

Detection of the Epstein-Barr virus in primary gastric lymphoma by in situ hybridization

The Epstein-Barr virus (EBV) has been shown to be associated with numerous human malignancies including Burktt's lymphoma and nasopharyngeal lymphoepithelioma. In addition, some typical gastric adenocarcinomas were also recently reported to demonstrate EBV relevance. The present study was designed to detect EBV in primary gastric lymphoma, using the in situ hybridization (ISH) method, in which oligo-nucleotide probes for the EBERl RNA and the EBV DNA W region have been used. Of the 49 cases of primary gastric lymphoma studied, which all showed B cell immunopheno-type, EBER1 sequences could only be found in four cases, including two low-grade cases and two high-grade cases of histological subtypes while the number of positive cells was less than 50% of the tumor cells. In one case of low-grade mucosa associated lymphoid tissue (MALT) lymphoma, the EBER1 -positive neoplastic cells were found in the regional lymph node, but the primary site of the stomach showed no positive signals. The EBV presence was further confirmed by the EBV DNA ISH. Using the ISH method, rare or occasional positive lymphoid cells (probably non-tumorous bystander cells) could be detected in 10 other cases including all histological subtypes. The present study shows that only a small proportion of primary gastric lymphoma is associated with EBV, and such positive cases could be found in both high- and low-grade histological subtypes. It is also suggested that the EBV presence in the neoplastic cells of some cases of primary gastric lymphoma is most likely a secondary phenomenon.     

广州地区EB病毒相关胃癌的临床病理特征及相关分子表达

目的 观察鼻咽癌高发区广州地区EB病毒相关胃癌的构成比、临床病理特征、EB病毒的潜伏类型,并初步探讨DNMT1、p16和cyclin D1在发病过程中的作用.方法 对676例胃癌采用组织芯片和EBER1原位杂交的方法筛选EB病毒相关胃癌,并用免疫组织化学EnVision法检测EB病毒潜伏期膜蛋白(LMP)和DNMT1、p16和cyclin D1的表达.结果 在676例胃癌中,45例EB病毒阳性(6.7%),EB病毒相关胃癌以男性为主,主要发生在胃的中上2/3,以弥漫型多见(P＜0.05).EBNA1和LMP2A的阳性例数分别为42例(93.3%)和24例(53.3%),EBNA2、LMP1和ZEBRA均未见表达.DNMT1、p16和cyclin D1在45例EB病毒相关胃癌的阳性例数分别为35例(77.8%)、10例(22.2%)和29例(64.4%),在40例EB病毒阴性胃癌的阳性例数分别为20例(50.0%)、25例(62.5%)和12例(30.0%),3个分子在两组胃癌的表达率差异均具有统计学意义(P＜0.05).p16与肿瘤的浸润深度有关(P＜0.05).LMP2A与DNMT1、DNMT1与p16、p16与cyclin D1存在相关关系(P＜0.05).结论 广州地区EB病毒相关胃癌占胃癌构成比的6.7%(45/676),EB病毒的潜伏类型部分为Ⅰ型,部分介于Ⅰ型和Ⅱ型之间.LMP2A、DNMT1、p16和cyclin D1的相互作用在EB病毒相关胃癌发生过程中起着重要的作用.     

Epstein-Barr virus genome polymorphisms of Epstein-Barr virus-associated gastric carcinoma in gastric remnant carcinoma in Guangzhou, southern China, an endemic area of nasopharyngeal carcinoma

Epstein-Barr virus (EBV) is associated with a subset of gastric carcinoma which was defined as EBV-associated gastric carcinoma (EBVaGC). The proportion of EBVaGC in gastric remnant carcinoma (GRC) was apparently higher than that in conventional gastric carcinoma (CGC) which occurs in the intact stomach. To clarify the possible mechanisms, 26 GRC cases from Guangzhou were investigated for the presence of EBV, and the EBV genome polymorphisms of EBVaGC in GRC were analyzed. Besides, the clinicopathologic characteristics, EBV latency pattern of EBVaGC in GRC were also investigated. Eight (30.8%) out of 26 cases were identified as EBVaGCs. Type A strain, prototype F, type I, mut-W1/I1, XhoI- and del-LMP1 variants were predominant among EBVaGC patients, accounting for 7 (87.5%), 7 (87.5%), 8 (100%), 6 (75%), 5 (62.5%) and 8 (100%) cases, respectively. All EBVaGC cases were male and with the histology of diffuse-type carcinoma. The tumor cells expressed EBNA1 (87.5%) and LMP2A (62.5%) but not LMP1, EBNA2 and ZEBRA. Thus, the EBV latency pattern was latency I. These were similar to those in CGC, except for the significantly higher proportion of EBVaGC in GRC than in CGC, suggesting that there is no more aggressive EBV variant in EBVaGC in GRC, and the injuries of gastric mucosa and/or changes of the microenvironment within the remnant stomach may be involved in the development of EBVaGC in GRC. This, to our knowledge, is the first study concerning about the EBV genome polymorphisms of EBVaGC in GRC in the world.     

No significant association of Epstein-Barr virus infection with invasive breast carcinoma

We studied 48 cases of invasive breast carcinoma for evidence of Epstein-Barr virus (EBV), which is associated with many human malignancies. In situ hybridization studies to detect the presence of EBV-encoded small nonpolyadenylated RNA (EBER)-1 were performed in paraffin sections. Immunohistochemical studies to detect EBV nuclear antigen (EBNA)-1, latent membrane protein (LMP)-1, and the transactivating immediate-early BZLF1 (ZEBRA) protein were also performed in paraffin sections. The presence of EBV genomic DNA was studied by polymerase chain reaction (PCR) amplification using sets of primers flanking the EBNA-4 and the EBV-LMP-1 genes in frozen tissues. Southern blot analysis using a probe flanking the EBV terminal repeat region was then attempted in cases that were PCR-positive. Five of 48 cases (10%) of breast carcinoma showed focal EBER-positive tumor cells. Twelve cases (25%) were positive for EBNA-1 by immunohistochemistry, all but one different from the EBER-positive cases. None of the cases were positive for LMP-1 or ZEBRA protein by immunohistochemistry. PCR studies for EBNA-4 and LMP-1 were each positive in five cases (including three cases in common). However, Southern blot studies successfully performed in all but one of the PCR-positive cases were completely negative. The identification of EBV by any methodology was not correlated with tumor size, grade, or lymph node status. This study demonstrated evidence of EBV infection in tissues involved by invasive breast carcinomas in a significant subset of cases. However, the lack of localization of EBV infection to a significant population of the tumor cells in any case, the negativity by Southern blot hybridization, and the lack of expression of multiple antigens in any case strongly argue against a significant role for EBV in the pathogenesis of breast carcinoma.     

Association of distinctive Epstein–Barr virus variants with gastric carcinoma in Guangzhou,southern China

To investigate the clinicopathologic features, Epstein–Barr virus (EBV) latency pattern and genome polymorphism of EBV‐associated gastric carcinoma (EBVaGC) in Guangzhou, an endemic area of nasopharyngeal carcinoma (NPC), an in situ hybridization assay of EBV‐encoded small RNA‐1 (EBER‐1) was used to identify the presence of EBV in 676 consecutive gastric carcinoma cases. EBV‐encoded proteins EBNA1, EBNA2, LMP1, and ZEBRA were detected by immunohistochemistry. EBV genome polymorphism was also analyzed by PCR and DNA sequencing. Of the 676 cases, 45 EBV‐positive cases (6.7%) were identified, including 37 (8.5%) male and 8 (3.3%) female cases. EBNA1 was detected in 42 cases (93.3%), while EBNA2, LMP1, and ZEBRA were all negative. In the EBV genome polymorphism analysis, type A strain, prototype F, type I, XhoI?, and del‐LMP1 variants were predominant among EBVaGC patients, accounting for 44 (97.8%), 37 (82.2%), 45 (100%), 34 (75.6%), and 42 (93.3%) cases, respectively. Moreover, a new hotspot mutation in the BamHI‐W1/I1 boundary region (148,972 T → C) was found in 39 (86.7%) of the 45 cases. The predominant EBV variants in EBVaGC in Guangzhou are prototype F, type I, and XhoI?, which are different from those in NPC in this area (predominant variant‐type “f”) and in EBVaGC in Latin American countries (predominant type “i” and XhoI+), suggesting that the EBV variants are not only geographically distributed but also disease restricted, and the pathogenic role of EBV in different EBV associated epithelial malignancies in different areas may be distinct. J. Med. Virol. 82:658–667, 2010. © 2010 Wiley‐Liss, Inc.     

Epstein-Barr virus in B-cell non-Hodgkin's lymphomas: Unexpected infection patterns and different infection incidence in low- and high-grade types

Two hundred and eight cases of B-cell non-Hodgkin's lymphoma (B-NHL) occurring in Europeans without any signs of HIV infection were investigated for their association with an Epstein-Barr virus (EBV) infection. The polymerase chain reaction (PCR) was applied for EBV-DNA detection, in situ hybridization (ISH) for the cellular localization of EBV-encoded small nuclear RNAs (EBER) and immediate-early RNAs (BHLF), and immunohistology (IH) for the detection of EBV-encoded latent membrane protein (LMP) and EBV nuclear antigen 2 (EBNA2) expression. PCR and EBER-ISH produced congruent results in those cases with amplifiable DNA. EBV was present overall in 26 per cent (54/208) of the B-NHL cases. Through EBER-ISH, the virus could be localized merely in rare non-neoplastic bystander lymphocytes in 27 and additionally in tumour cells of 27 cases. Unexpectedly, the proportion of EBV-infected tumour cells present in the different cases varied between 1 and 100 per cent. All but three of the cases with infected tumour cells were of high-grade malignancy. Correlation with the morphological and immunological tumour phenotype revealed that all cases with more than 80 per cent EBER-positive tumour cells were either B-anaplastic large cell lymphomas (B-ALCL), sporadic Burkitt's lymphomas, or B-NHLs with partial or full plasmacellular differentiation. LMP was consistently absent from Burkitt's lymphomas and constantly expressed in B-ALCLs with EBER-positive tumour cells, while in all other instances it varied greatly and was rarer than EBER expression. The above findings suggest that in cases where EBV is present in 80–100 per cent of tumour cells, EBV infection takes place before malignant transformation and thus may have contributed to the malignant phenotype, whereas in the other cases with only a smaller number of infected tumour and single bystander cells, EBV infection may have occurred following malignant transformation. In these cases, infection would appear to be of little or no significance in tumourigenesis.     

Frequent presence of latent Epstein-Barr virus infection in lymphoepithelioid cell lymphoma (Lennert's lymphoma)

This study deals with the investigation of the biological significance of an Epstein–Barr virus (EBV) infection in lymphoepithelioid cell lymphoma. A selection of EBV-detection techniques was applied to 15 cases, including polymerase chain reaction (PCR) for the detection of EBV-DNA, in situ hybridization (ISH) for the cellular localization of EBV-encoded small nuclear (EBER 1 and EBER 2) and immediate-early (BHLF) RNAs, and immunohistology for the detection of EBV-encoded latent membrane protein (LMP) expression. PCR and EBER-ISH produced congruent results in those cases with amplifiable DNA, leading to an EBV presence in 11/15 lymphoepithelioid cell lymphoma cases (73%). EBER-ISH combined with immunohistology localized the virus predominantly in several B immunoblasts and small B lymphocytes in eight of the EBV-positive cases, five of which also contained single infected lymphocytes expressing T-cell characteristic antigens. LMP was detected using immunohistology in only a proportion of immunoblasts in four of these cases. The remaining three EBV-positive lymphoepithelioid cell lymphoma cases contained only single EBER-positive small B lymphocytes without LMP expression. No case contained BHLF-RNA expressing cells. These data imply that, although latently EBV-infected cells are frequently present in lymphoepithelioid cell lymphoma cases, the virus is probably not directly involved in the pathogenesis of this entity.     

Correlation of the expression of Epstein-Barr virus latent membrane protein and in situ hybridization with biotinylated BamHI-W probes in Hodgkin''s disease.

The detection of Epstein-Barr virus (EBV) nucleic acids by in situ hybridization (ISH) with biotinylated BamHI-W probes was correlated with the expressions of EBV latent membrane protein (LMP) and EB nuclear antigen 2 (EBNA2), in 107 cases of Hodgkin's disease (HD) of different immunomorphologic subtypes. Epstein-Barr virus nucleic acids were present and restricted to the pathogenic cells in 4 of 40 (10%) cases of nodular sclerosis (NS) and 33 of 55 (60%) cases of mixed cellularity (MC), but were undetectable in other subtypes. Of the 37 cases positive for EBV nucleic acids, 35 (95%) showed the expression of LMP. Epstein-Barr virus nucleic acids and LMP were restricted to Reed-Sternberg cells and variants. Only 1 case (MC) showed LMP expression in the absence of EBV detection. The correlation was strengthened by the finding of LMP expression at first diagnosis in 6/7 EBV positive cases at relapse (14-126 months) (5/5 EBV negative cases at relapse were LMP negative at first diagnosis). EBNA2 was absent in all 13 (NS, 2; MC, 11) EBV+ and LMP+ cases tested. Both LMP and EBNA2 were expressed in control EBV-positive tissues and cell lines. EBV serology in MC HD was indicative of latent EBV infection, but neither serology nor clinical parameters correlated with the presence or the absence of EBV, over a short-term follow-up (median, 20 months). The findings, although not proving EBV as the etiologic agent of HD, suggest that: 1) LMP expression alone may be adequate for identifying EBV-associated HD, 2) the MC subtype has a stronger relation with EBV presence, and 3) the regulation of EBV genes in HD is different from other EBV-associated disorders. The clinical implications still remain to be discovered.     

CLINICOPATHOLOGICAL,IMMUNOLOGICAL AND GENETIC STUDIES OF CD30+ ANAPLASTIC LARGE CELL LYMPHOMA OF B-CELL TYPE; ASSOCIATION WITH EPSTEIN–BARR VIRUS IN A JAPANESE POPULATION

The clinicopathological features, the immunophenotype, and the presence of Epstein–Barr virus (EBV)-associated genomes and gene products were examined in 17 cases of CD30⁺ anaplastic large cell lymphoma (ALCL) of B-cell type. Microscopically, the 17 cases were divided into ten cases of the monomorphic type and seven cases of the pleomorphic type. EBV was detected in 6 of 17 cases (38 per cent) by RNA in situ hybridization (ISH) with EBV-encoded RNA (EBER1). EBER1⁺ cases consisted of two cases (20 per cent) of the monomorphic type and four cases (57 per cent) of the pleomorphic type. The five EBER1⁺ cases showed clonality of the EBV genome by Southern blotting, consistent with the presence of EBV in a monoclonal proliferation. The EBV-encoded latent membrane protein 1 (LMP1) was found in all six EBER1⁺ cases and EBV-encoded nuclear antigen 2 (EBNA2) was present in two cases by immunohistochemistry. No expression of LMP1 or EBNA2 was observed in the EBER1⁻ cases. The EBER1⁺ cases had a tendency for a more favourable prognosis than the EBER1⁻ cases. It is concluded that EBV has an association with CD30⁺ ALCL of B-cell type in the Japanese population studied, and especially with the large pleomorphic type. EBV infection may play a pathoaetiological role and may influence clinical behaviour.     

Detection of Epstein-Barr virus-infected mucosal lymphocytes in nasal polyps.

Primary nasal lymphomas of T or NK cell origin are known to be associated with Epstein-Barr virus (EBV). However, it is not known whether EBV is normally present in nasal mucosa as distinct to nasopharyngeal tissue. This study investigates the prevalence of EBV infection in 13 cases of nasal polyps. EBV DNA was detected in 2 of 13 (15%) by Southern blot hybridization and in 9 of 13 (69%) by polymerase chain reaction. In situ hybridization for EBV-encoded small nuclear RNAs (EBER) was positive in 11 of 13 (85%) cases; the virus was present in stromal lymphocytes only and not in the epithelial cells. Immunohistochemistry for EBV proteins in 7 cases revealed EBV nuclear antigen (EBNA)-2, latent membrane protein (LMP)-1, and ZEBRA (the switch protein encoded by gene BZLF1) expression in rare isolated stromal lymphocytes in 3 cases. Double immunostaining in 1 case showed that the LMP-1+ cells were B or T cells. Immunohistochemistry for EBV lytic proteins showed very rare viral capsid antigen (VCA)+ and membrane antigen (MA)+ cells in 1 case and very rare diffuse early antigen (EA-D)+ and VCA+ cells in 1 other case. The expression of ZEBRA, EA-D, VCA, and MA suggested a disruption of latency in very rare stromal lymphocytes leading to a productive cycle. Although the incidence of EBV positivity in nasal polyps in our population is high (85%), very low numbers of EBV+ cells are found in each case. Nevertheless, they indicate that nasal mucosa could be one of the sites of EBV persistence through a low level of infection of the resident lymphocytes and thereby provide a possible setting for the emergence of virally associated tumors in this site.     

Sporadic EBV-associated lymphoepithelial salivary gland carcinoma with EBV-positive low-grade myoepithelial component

Salivary gland lymphoepithelial carcinomas (LECs) are associated with Epstein–Barr virus (EBV) in endemic areas, whereas sporadic cases are usually EBV negative. We have studied two EBV-associated LECs from Caucasian patients for their EBV gene expression profile and their immunophenotype. Tumour cells of case 1 showed expression of EBNA1 only, corresponding to an EBV latency type I. Tumour cells of this case expressed various basal and glandular cytokeratins. In case 2, the LEC was accompanied by a low-grade spindle cell lesion with an immunophenotype of myoepithelial cells, whereas the high-grade tumour expressed cytokeratin (Ck) 8 only. In case 2, the high-grade tumour showed an EBV lantency II pattern with expression of EBNA1, LMP1 and LMP2A (latency II). The spindle cell lesion of this case was also EBV-infected and showed low levels of EBNA1 and LMP1 expression, while LMP2A was not detectable. The detection of EBV in both components of case 2 together with immunophenotypic evidence of transition between both components supports the notion that at least some LECs arise through a low-grade myoepithelial intermediate. Expression of LMP2A may be of therapeutic interest because it may make such cases amenable to immunotherapy with EBV-specific cytotoxic T cells.     

Epidemiological study, immunohistochemistry and in situ hybridization studies of nasopharyngeal carcinomas: a Tunisian report

Nasopharyngeal carcinomas (NPC) are a significant problem of public health in Tunisia. They are particular because of their characteristic geographic distribution. The aims of this study were, first, to appreciate the presence of Epstein-Barr virus (EBV) genome by immunohistochemistry (IHC) and in situ hybridization (ISH) and to compare their benefits to NPC diagnosis and, secondly, to verify the relation between NPC and factors bound to the food and environment conditions. Biopsies, recruited at the department of pathology of EPS Charles Nicolle at Tunis, were analyzed for EBV genome presence by ISH of EBV-encoded small RNA1 (EBER1). IHC was done with encoded nuclear antigen (EBNA1), latent membrane proteins (LMP1), and antigen BZ1 anti-Z EBV-replication activator (ZEBRA). An epidemiological study based upon the analysis of a detailed questionnaire submitted to patients (all from the north of Tunisia) and 60 witnesses was done. The statistic analysis was realised by SPSS Windows 11.5 Advanced Statistics. All samples were classified as Undifferentiated Carcinoma of Nasopharyngeal type (UCNT). We found a sex ratio of 2 with a bimodal repartition. ISH showed 96.6% positive samples. IHC revealed the EBV in 90% of cases and 66.7%, respectively, with EBNA1 and LMP1. The statistic analysis showed a meaningful relation (P<0.05, OR>3) between NPC and dietary factors (spices and piquant condiment), alcohol and the water quality.     

Frequent expression of the tumor necrosis factor receptor-associated factor 1 in latent membrane protein 1-positive posttransplant lymphoproliferative disease and HIV-associated lymphomas

The tumor necrosis factor receptor-associated factor 1 (TRAF1) participates in the signal transduction of various members of the tumor necrosis factor receptor (TNFR) family, including TNFR2, CD40, CD30, and the Epstein-Barr virus (EBV)-encoded latent membrane protein 1 (LMP1). In vitro, TRAF1 is induced by LMP1, and previous studies have suggested that expression of TRAF1 is higher in EBV-associated tumors than in their EBV-negative counterparts. To determine whether this was the case in posttransplant lymphoproliferative disease (PTLD) and related disorders, we used immunohistochemistry to analyze expression of TRAF1 in a total of 42 such lesions arising in a variety of immunosuppressive states. The specimens consisted of 22 PTLD lesions, 18 acquired immunodeficiency syndrome-associated lymphomas, including 6 primary central nervous system lymphomas, and 2 cases of Hodgkin disease. The presence of latent EBV infection was determined by EBER in situ hybridization, and expression of EBV-LMP1 was detected by immunohistochemistry. Latent EBV infection, as determined by a positive EBER signal, was detected in 36 of 42 tumors. Of the EBER-positive specimens, 30 of 36 also expressed LMP1. Twenty-four of 30 LMP1-positive tumors, including both Hodgkin disease specimens, expressed TRAF1, compared with only 3 of 12 LMP1-negative tumors. This difference was statistically significant (P <.005). These results show frequent expression of TRAF1 at the protein level in LMP1-positive PTLD and related disorders and suggest an important role for LMP1-mediated TRAF1 signaling in the pathogenesis of EBV-positive tumors arising in immunosuppressive states.     

Characteristics of Epstein-Barr virus associated childhood non-Hodgkin’s lymphoma in the Republic of Korea

To analyze the clinicopathologic characteristics of childhood non-Hodgkins lymphoma (NHL) associated with Epstein-Barr virus (EBV), EBER in situ hybridization was performed in 80 cases of NHLs. EBER-positive lymphomas account for 25% (20/80) and include NK/T-cell lymphoma (6/6), aggressive NK-cell leukemia (1/1), peripheral T cell lymphoma (5/11), diffuse large B-cell lymphoma (5/14), hydroa-like T-cell lymphoma (1/1), marginal zone B-cell lymphoma (1/2), and post-transplantation lymphoproliferative disorder (1/1). Other types including 19 cases of Burkitts lymphoma were negative. For 9 EBER-positive cases, immunohistochemical staining for LMP-1, and EBNA-2 was performed to determine the EBV latency pattern. Two of nine EBER-positive cases expressed both LMP-1 and EBNA-2. Clinically, patients with EBV-positive B-cell lymphomas were cured with chemotherapy, whereas EBV-associated NK- and T cell lymphomas pursued fatal clinical course. In conclusion, EBVs infected in childhood NHLs are frequently associated not only with NK- and T- cell lymphomas but also large B-cell lymphomas.