Epstein‐Barr virus infection in the neoplastic and nonneoplastic cells of lymphoid malignancies

Teramoto, Norihiro; Sarker, Ashit Baran; Tonoyama, Yuji; Yoshino, Tadashi; Hayashi, Kazuhiko; Takahashi, Kiyoshi; Akagi, Tadaatsu

doi:10.1002/(sici)1097-0142(19960601)77:11<2339::aid-cncr24>3.3.co;2-p

Cited by 9 publications

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“…EBERISH was performed as reported previously (Teramoto et al, 1996). Deparaffinized sections were treated with 0.2 N HCl for 10 minutes and then with 5 g/ml proteinase K in 50 mM Tris-HCl (pH 8.0) at 37°C for 15 minutes.…”

Section: In Situ Hybridization and Immunostainingmentioning

confidence: 99%

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Epstein-Barr Virus Infection to Epstein-Barr Virus-Negative Nasopharyngeal Carcinoma Cell Line TW03 Enhances Its Tumorigenicity

Teramoto

Maeda

Kobayashi

et al. 2000

Laboratory Investigation

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SUMMARY:Almost all nasopharyngeal carcinomas (NPCs) are infected by Epstein-Barr virus (EBV), but most ex vivo NPC cells lose EBV genomes during passages. In this study, an EBV-negative NPC cell line, TW03, established from EBV-carrying NPC was reinfected with EBV by cocultivation with irradiated Akata cells carrying recombinant EBV containing a neomycin-resistant gene. The reinfected EBV (ϩ) TW03 cells expressed EBERs and EBNA1, but not EBNA2, lytic proteins (ZEBRA and EA-D), or LMP1. They had an epithelial appearance similar to that of EBV (Ϫ) TW03 cells. The doubling times of EBV (ϩ) and EBV (Ϫ) TW03 cells were almost identical. However, the EBV (ϩ) TW03 cells formed larger colonies with ragged contours in anchorage-independent cultures. An in vitro invasion assay showed that EBV (ϩ) TW03 cells had a higher invasive activity than EBV (Ϫ) TW03 cells (p Ͻ 0.01). Both EBV (Ϫ) and EBV (ϩ) TW03 cells formed poorly differentiated squamous cell carcinomas in SCID and nude mice. EBV (ϩ) TW03 cells showed a higher tumorigenicity to nude mice (12 of 13) than EBV (Ϫ) TW03 cells (1 of 9) (p Ͻ 0.001). In the severe combined immunodeficiency (SCID) tumors of EBV (ϩ) TW03 cells, not all of the tumor cells were EBER-1 positive. EBER-1 was more frequently detected in the peripheral regions and daughter nodules of the tumors than in the central areas. The microdissection polymerase chain reaction showed that the EBER-1-negative TW03 cells in the EBV (ϩ) TW03 SCID tumors lost EBV genomes. EBER-1-negative cells showed as high a rate of Ki-67 positivity as EBER-1-positive cells, indicating that the former were proliferating rather than dead or dying. In horny pearls, keratinizing cells were ZEBRA-positive and EBER-negative. Loss of EBV genomes was not associated with squamous differentiation. These data indicated that reinfection of EBV promotes the tumorigenicity of EBV (Ϫ) TW03 cells by enhancing the invading activity. (Lab Invest 2000, 80:303-312).

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Section: In Situ Hybridization and Immunostainingmentioning

confidence: 99%

“…An antigen retrieval procedure was performed if necessary. Simultaneous immunostaining against Ki-67 or cytokeratin and EBERISH was performed as described previously (Teramoto et al, 1996). Staining with EBERISH was performed first and then the specimens were subjected to immunostaining.…”

Section: In Situ Hybridization and Immunostainingmentioning

confidence: 99%

Epstein-Barr Virus Infection to Epstein-Barr Virus-Negative Nasopharyngeal Carcinoma Cell Line TW03 Enhances Its Tumorigenicity

Teramoto

Maeda

Kobayashi

et al. 2000

Laboratory Investigation

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“…10,11 Epstein-Barr virus (EBV), the etiologic agent of infectious mononucleosis, has been linked to a wide range of tumors, mainly of B-cell origin. 12 Association of PTCLs with EBV has been first described in the late 1980s, 13 and has since been found to be present in an important fraction of cases in series from Asia [14][15][16][17][18][19] and from Western countries. [20][21][22][23] While some entities (angioimmunoblastic T-cell lymphoma 24 and extranodal NK/Tcell lymphoma, nasal type 25 ) are almost systematically associated with EBV, the frequency and signification of such an association among others is less well defined.…”

Section: Introductionmentioning

confidence: 99%

“…The EBER-ISH technique was found to be positive in 41% of patients, again paralleling the results of previous studies. 14,[17][18][19][20] The high sensitivity of the EBER-ISH technique compared with immunostaining, even in archival material, is well known 14,17,18,20 and illustrated here by the fact that LMP-1 was positive in only half of the EBER-ISHpositive cases.Although the type of treatment varied between protocol arms, all but one patient (109/110) were treated with an anthracyclinbased regimen. All patients 60 years or younger received an intensive regimen with curative intent.…”

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confidence: 99%

Prognostic significance of Epstein-Barr virus in nodal peripheral T-cell lymphoma, unspecified: a Groupe d'Etude des Lymphomes de l'Adulte (GELA) study

Dupuis¹,

Émile²,

Mounier³

et al. 2006

Blood

122

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Peripheral T-cell lymphomas (PTCLs) are rare and have a dismal prognosis. The most frequent subtype is PTCL, unspecified. Epstein-Barr virus (EBV) has been detected in around 40% of cases, but its prognostic significance is not fully established. Lymph node samples from 110 patients with PTCL, unspecified included in LNH87 and LNH93 trials were available. EBV status was studied by EBV-encoded small RNA in situ hybridization (EBER-ISH). EBER-ISH showed positive cells in 45 (41%) of 110 patients. Pretreatment characteristics were comparable between positive and negative cases, except for male sex (80% versus 60%, respectively, P ‫؍‬ .02). Only 50% of patients achieved complete remission with a 5-year eventfree survival (EFS) and overall survival (OS) of 21% and 30%, respectively. EBER-ISH positivity was the sole factor linked with worse EFS, with a 5-year probability of 11% for positive patients. In univariate analysis, factors affecting OS were EBER-ISH positivity, high LDH level, and age older than 60 years. In multivariate analysis, EBER-ISH was associated with a worse OS in the elderly population. Timedependent analysis showed that the negative impact of EBV was essentially seen in the first 2 years following diagnosis. These results warrant further studies regarding pathogenesis and specific treatment approaches for EBV-associated PTCL patients. IntroductionT-cell lymphomas are rare in Europe and the United States, where they represent around 15% of non-Hodgkin lymphomas. 1,2 As we and others have shown, a T-cell immunophenotype (except for anaplastic large cell lymphoma) is an independent predictor of poor prognosis in aggressive lymphomas. 1,3,4 The WHO classification of lymphoid tumors recognizes 16 different entities among peripheral (mature) T-and natural killer (NK)-cell neoplasms. 5 Among these, the entity peripheral T-cell lymphoma, unspecified (PTCL-U) accounts for about half the cases of PTCL seen in Western countries. 3,6-8 PTCL-U forms a heterogeneous group of predominantly nodal (and occasionally extranodal) diseases that do not fit into the definition of any other recognizable subtype of PTCL. Although their histopathological aspect is highly variable, usual morphologic characteristics include pleomorphic cellular composition, and frequently a polymorphous inflammatory background. 5 Most cases display a CD4 ϩ /CD8 Ϫ helper T-cell phenotype, less frequent cases showing a cytotoxic CD4 Ϫ /CD8 ϩ /TIA1 ϩ /granzyme B ϩ phenotype, which has been linked by certain authors to a worse outcome. 9 Efforts to identify different entities with pathophysiologic and prognostic significance among PTCL-U are ongoing. 10,11 Epstein-Barr virus (EBV), the etiologic agent of infectious mononucleosis, has been linked to a wide range of tumors, mainly of B-cell origin. 12 Association of PTCLs with EBV has been first described in the late 1980s, 13 and has since been found to be present in an important fraction of cases in series from Asia [14][15][16][17][18][19] and from Western countries. [20][21][22][23] While some...

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“…The EBV-encoded small RNA-1 (EBER-1) was detected by EBER-ISH in formalin-fixed, paraffin-embedded liver biopsy specimens [41]. Briefly, the 5-pm-thick sections were deparaffinized, treated with 0.2 N HCI for 10 min at room temperature and with 5yg of proteinase K (Sigma, St.Louis, Mo., USA) for 15 min at 37°C.…”

Section: Epstein-barr Virus Genome Analysesmentioning

confidence: 99%

Polymerase chain reaction and in situ hybridization of Epstein-Barr virus in liver biopsy specimens facilitate the diagnosis of EBV hepatitis after liver transplantation

Barkholt¹,

Reinholt

Teramoto

et al. 1998

Transplant Int

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A nested polymerase chain reaction (nPCR) for EpsteinBarr virus (EBV) DNA, RNA in situ hybridization (EBER-ISH), and immunostaining against the ZEBRA EBV protein for diagnosis of EBV hepatitis were performed on 43 liver biopsy specimens obtained from 18 patients in the 1st year after liver transplantation (LTX). The findings were related to liver histology and results of EBV-nPCR on concomitantly obtained serum samples. EBV DNA was detected in 30 YO and RNA in 34 Y of the liver biopsy specimens using nPCR and EBER-ISH, respectively, giving a significant correlation between the two methods ( P = 0.003). All but one patient had detectable EBV DNA in serum samples obtained within 1 month of the biopsy. More than 90 YO of the nPCR and EBER-ISH-positive biopsy specimens were obtained 3 months or less post-LTX. There was no significant difference in EBV genome findings in biopsy specimens with or without lymphocytic-immunoblastic infiltrates, either in nPCR ( P = 0.73) or in ISH ( P = 0.73). Two of three biopsy specimens with these histological changes suggesting a viral genesis were positive in EBVnPCR but negative in ISH. Histopathological changes in EBV hepatitis may be nonspecific and masked by other complications. The use of EBV-nPCR and EBER-ISH in liver graft biopsy specimens of heavily immunosuppressed patients may give an early indication of EBV-related disease and can be used to guide therapeutic intervention.

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Epstein‐Barr virus infection in the neoplastic and nonneoplastic cells of lymphoid malignancies

Abstract: of Lymphoid Ma I i g n a ncies BACKGROUND. The Epstein-Barr virus (EBV) has been frequently detected in

Cited by 9 publications

References 0 publications

Epstein-Barr Virus Infection to Epstein-Barr Virus-Negative Nasopharyngeal Carcinoma Cell Line TW03 Enhances Its Tumorigenicity

Epstein-Barr Virus Infection to Epstein-Barr Virus-Negative Nasopharyngeal Carcinoma Cell Line TW03 Enhances Its Tumorigenicity

Prognostic significance of Epstein-Barr virus in nodal peripheral T-cell lymphoma, unspecified: a Groupe d'Etude des Lymphomes de l'Adulte (GELA) study

Polymerase chain reaction and in situ hybridization of Epstein-Barr virus in liver biopsy specimens facilitate the diagnosis of EBV hepatitis after liver transplantation

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