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>3.0.co;2-x

Cited by 22 publications

(5 citation statements)

References 23 publications

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“…4,5,10,11 Multiple studies have looked for the presence of EBV (i.e., EBER) in PTCL tumor tissue with variable results. [12][13][14][15][16][17][18][19][20][21][22][23][24] The incidence of EBV-associated PTCL differ substantially worldwide, 25 and studies focused on North American and European populations are limited. Some studies have suggested a worse survival in EBER1 PTCL.…”

Section: Introductionmentioning

confidence: 99%

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Frequency and clinical correlates of elevated plasma Epstein‐Barr virus DNA at diagnosis in peripheral T‐cell lymphomas

Haverkos¹,

Huang

Gru

et al. 2017

Intl Journal of Cancer

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Epstein Barr virus (EBV)-encoded RNAs (EBER) in tumor tissue and cell-free plasma EBV-DNA (pEBVd) are detected in EBV-associated lymphomas. Studies have suggested that EBER+ peripheral T-cell lymphomas (PTCL) have worse prognosis, but the role of EBV in these neoplasms remains unclear. pEBVd is quantitative and more easily amenable to standardization than EBER, but frequency of pEBVd detection, clinical impact, and agreement with EBER status in PTCL are unknown. We retrospectively assessed frequency of detectable pre-treatment pEBVd, presence of EBER in tumor tissue, and outcomes in 61 of 135 EBV-assessable PTCL patients. Fifteen of 61 patients (24.5%, 95% CI: 14–37%) were pre-treatment pEBVd+, with no significant differences in baseline characteristics or treatment between pEBVd+ and pEBVd− patients. EBER-ISH was performed on 10 pEBVd+ and 35 pEBVd− tumors. All 10 pEBVd+ patients were EBER+, but 9 pEBVd− patients were also EBER+. With median follow up of 24 months (range 1–96), overall survival (OS) was shorter in pEBVd+ compared to pEBVd− patients (13 vs. 72 months; p=0.04). In this retrospective study, pre-treatment pEBVd was elevated in 25% of PTCL patients, was highly specific for EBER+ tumors, and was associated with shorter survival. pEBVd should be further explored as a prognostic variable and tumor biomarker in PTCL.

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Section: Introductionmentioning

confidence: 99%

“…Multiple studies have looked for the presence of EBV (i.e., EBER) in PTCL tumor tissue with variable results . The incidence of EBV‐associated PTCL differ substantially worldwide, and studies focused on North American and European populations are limited.…”

Section: Introductionmentioning

confidence: 99%

Frequency and clinical correlates of elevated plasma Epstein‐Barr virus DNA at diagnosis in peripheral T‐cell lymphomas

Haverkos¹,

Huang

Gru

et al. 2017

Intl Journal of Cancer

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“…2 Most EBV-related lymphomas are of a B-cell lineage; however, a subset of NK and T-cell lymphomas are also associated with EBV. 3,4 Specifically recognized B-cell lymphomas associated with EBV include classical Hodgkin lymphoma, Burkitt lymphoma, lymphomatoid granulomatosis, post transplant and other lymphoproliferative disorders associated with immunodeficiency, and subsets of diffuse large B-cell lymphoma. Large B-cell lymphomas associated with EBV are usually aggressive neoplasms and include several subtypes: plasmablastic lymphoma, diffuse large B-cell lymphoma associated with chronic inflammation, primary central nervous system lymphoma arising in immunosuppressed patients, and EBV-positive diffuse large B-cell lymphoma.…”

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confidence: 99%

Epstein-Barr virus-positive follicular lymphoma

et al. 2017

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Epstein-Barr virus (EBV) -associated follicular lymphoma is only rarely reported. Herein, we report the largest series analyzing prevalence and clinicopathologic characteristics of EBV-associated follicular lymphoma occurring in unselected cases. Out of 382 analyzed cases, 10 EBV-positive follicular lymphomas were identified (prevalence=2.6%, 95% confidence interval 1.3-4.0%). All EBV-positive follicular lymphomas showed EBV-encoded small RNA-positive lymphoma cells present in a follicular distribution. Of these, eight also had tissue available for testing of expression of latent membrane protein 1 (LMP1), out of which six (75%) were positive. There was a significant association with grades 3A-3B follicular lymphoma (P<0.0001) and CD30 expression (P=0.0002). EBV-positive follicular lymphomas were otherwise morphologically and immunophenotypically indistinguishable from EBV-negative cases of similar grade. Nine of the EBV-positive follicular lymphomas occurred in patients with no known history of immunosuppression, while one patient had a history of hydroxychloroquine administration for Sjögren's syndrome. The mean age in the EBV-positive and -negative follicular lymphomas was 56 (range 31-83 years) and 49 years (range 25-92 years), respectively, with no statistically significant difference. Seven of the patients with EBV-positive follicular lymphoma had additional biopsies from different time points available for review, all of which showed progression of disease in the form of progression of tumor grade. Five of these progressed to diffuse large B-cell lymphoma, one of which had tissue available for testing and was EBV-positive. Our findings suggest that EBV infection may have a role in lymphomagenesis and/or disease progression in a subset of follicular lymphomas, thereby expanding the spectrum of recognized EBV-associated B-cell lymphomas.

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“…The presence of LDH in the cell reflects an alteration in the metabolic pathways towards that of anaerobic glycolysis (Bloom et al, 1967;Pan et al, 1991), and its release from PBMC has been described but without detailed investigation in association with malignancies (Decker & Lohmann-Matthes, 1988;. As the greatest LDH release is observed in patients with HD, this might be linked to the association of HD with EBV, in Reed-Sternberg cells, and in a variable proportion of nonneoplastic lymphoid cells (Valente et al, 1994;Teramoto et al, 1996;Anagnostopoulous et al, 1996).…”

Section: Discussionmentioning

confidence: 99%

The difference in NK‐cell activity between patients with non‐Hodgkin's lymphomas and Hodgkin's disease

et al. 1999

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Summary. Natural killer (NK) cells play an important role in immune surveillance against malignant diseases. Considering the lymphoid origin of malignant lymphomas, as well as scarce data concerning NK-cell function in these neoplasms, we evaluated NK-cell activity in 49 patients with nonHodgkin's lymphomas (NHL) and 47 patients with Hodgkin's disease (HD), prior to therapy. Using the recommended International Working Formulation and the Ann Arbor staging system for classification of lymphomas we found, by the LDH release cytotoxicity assay, that decreased NK-cell activity (P < 0·05) in NHL patients was essentially related to unfavourable histology (13 indolent lymphomas, 25 intermediate and 11 very aggressive lymphomas were included), but that within these categories clinical stage of the disease also contributed to the degree of NK-cell dysfunction. In contrast, in HD, NK-cell activity was persistently decreased (P < 0·05), compared to controls, irrespective of histological type and clinical stage. It is of interest also that the most profound NK-cell dysfunction that is present and persistent from the onset of HD, and which appears in very aggressive NHL was associated with the phenomenon of increased spontaneous lactate acid dehydrogenase (LDH) release activity from the separated PBMC of these patients. The difference in the level of NK-cell impairment between patients with various histological grades of malignancy in NHL and HD suggests different initial participation of innate immune reactions in these diseases.

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

Cited by 22 publications

References 23 publications

Frequency and clinical correlates of elevated plasma Epstein‐Barr virus DNA at diagnosis in peripheral T‐cell lymphomas

Frequency and clinical correlates of elevated plasma Epstein‐Barr virus DNA at diagnosis in peripheral T‐cell lymphomas

Epstein-Barr virus-positive follicular lymphoma

The difference in NK‐cell activity between patients with non‐Hodgkin's lymphomas and Hodgkin's disease

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