EBV latent membrane protein 1 abundance correlates with patient age but not with metastatic behavior in north African nasopharyngeal carcinomas

Khabir, Abdelmajid; Karray, H.; Rodriguez, S.; Rosé, Mathieu; Daoud, J.; Frikha, M.; Boudawara, T.; Middeldorp, Jaap M.; Jlidi, R.; Busson, P.

doi:10.1186/1743-422x-2-39

Cited by 63 publications

(25 citation statements)

References 31 publications

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“…There was a borderline significant relationship between LMP1 expression and T stage ( P = 0.042), but not with N and M stages. The intensity score of EBV-LMP1 expression in this study was somewhat lower than others[30]. Higher LMP1 expression in patients < 30 years old was associated with more locoregional progressivity at young age.…”

Section: Resultscontrasting

confidence: 80%

“…Details of the EBV-related diagnostic results in our patients will be published elsewhere. In a selected group of juvenile and adult cases that were matched for TNM stage and sex and confirmed to be EBV positive by EBER-RISH using commercial reagents, we also analyzed the expression of latent membrane protein 1 (LMP1) using OT21C monoclonal antibody-based immunohistochemistry on paraffin-embedded tissue sections, as described before[29],[30].…”

Section: Case Definition and Historical Analysismentioning

confidence: 99%

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Nasopharyngeal carcinoma in Indonesia: epidemiology, incidence,signs, and symptoms at presentation

Adham¹,

Kurniawan²,

Muhtadi³

et al. 2012

Chin J Cancer

294

295

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Among all head and neck (H&N) cancers, nasopharyngeal carcinoma (NPC) represents a distinct entity regarding epidemiology, clinical presentation, biological markers, carcinogenic risk factors, and prognostic factors. NPC is endemic in certain regions of the world, especially in Southeast Asia, and has a poor prognosis. In Indonesia, the recorded mean prevalence is 6.2/100 000, with 13 000 yearly new NPC cases, but otherwise little is documented on NPC in Indonesia. Here, we report on a group of 1121 NPC patients diagnosed and treated at Dr. Cipto Mangunkusumo Hospital, Jakarta, Indonesia between 1996 and 2005. We studied NPC incidence among all H&N cancer cases (n=6000) observed in that period, focusing on age and gender distribution, the ethnic background of patients, and the disease etiology. We also analyzed most prevalent signs and symptoms and staging of NPC patients at first presentation. In this study population, NPC was the most frequent H&N cancer (28.4%), with a male-to-female ratio of 2.4, and was endemic in the Javanese population. Interestingly, NPC appeared to affect patients at a relatively young age (20% juvenile cases) without a bimodal age distribution. Mostly, NPC initiated in the fossa of Rosenmuller and spreaded intracranially or locally as a mass in the head. Occasionally, NPC developed at the submucosal level spreading outside the anatomic limits of the nasopharynx. At presentation, NPC associated with hearing problems, serous otitis media, tinnitus, nasal obstruction, anosmia, bleeding, difficulty in swallowing and dysphonia, and even eye symptoms with diplopia and pain. The initial diagnosis is difficult to make because early signs and symptoms of NPC are not specific to the disease. Early-age Epstein-Barr virus (EBV) infection combined with frequent exposure to environmental carcinogenic co-factors is suggested to cause NPC development. Undifferentiated NPC is the most frequent histological type and is closely associated with EBV. Expression of the EBV-encoded latent membrane protein 1(LMP1) Oncogene in biopsy material was compared between NPC patients of < 30 years old and those of ≥ 30 years old, matched for sex and tumor stage. Higher LMP1 expression in patients of <30 years old was observed, which was related to more locoregional progressivity. Increased medical awareness of prevailing early stage signs and symptoms coupled to use of EBV-related diagnostic tumor markers may lead to down-staging and timely treatment to improve survival of patients with this aggressive disease.

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Section: Resultscontrasting

confidence: 80%

Section: Case Definition and Historical Analysismentioning

confidence: 99%

Nasopharyngeal carcinoma in Indonesia: epidemiology, incidence,signs, and symptoms at presentation

Adham¹,

Kurniawan²,

Muhtadi³

et al. 2012

Chin J Cancer

294

295

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show abstract

“…Both LMP1 and LMP2 are able to avoid immune recognition [20, 21]. Despite these hurdles, both LMP1 and LMP2 have high expression in NPC and are relatively immunogenic [22, 23], rendering them suitable candidates for EBV-targeted immunotherapy. In this study, we demonstrate that LMP1-based DNA vaccine elicits LMP1-specific CTL activities and suppresses/prevents LMP1-expressing tumor development in murine models.…”

Section: Discussionmentioning

confidence: 99%

Therapeutic vaccine targeting Epstein-Barr virus latent protein, LMP1, suppresses LMP1-expressing tumor growth and metastasis in vivo

Lin

Chen

et al. 2017

BMC Cancer

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BackgroundIn endemic area, nasopharyngeal carcinoma (NPC) tumor cells harbor EBV latent infection and expresses viral antigens such as EBNA1, LMP1 and LMP2. In this study, we established a NPC-mimicry animal model and assessed the therapeutic potential of LMP1 vaccine.MethodsAnimal models were established by injection of LMP1-expressing TC-1 cells in C57BL6/J mice subcutaneously or through tail veins. pcDNA3.1 empty vector or LMP1/pcDNA3.1 vaccine was delivered by a helium-driven gene gun. Effectiveness of vaccine was evaluated by measuring the tumor size and numbers of metastatic lung nodules. Circulating cytokines were evaluated by ELISArray. Populations of activated cytotoxic T lymphocytes (CTLs) and LMP1-specific T lymphocytes were evaluated by flow cytometry with CD8/CD107a double staining and interferon-γ ELISPOT assay, respectively.ResultsLMP1 vaccine significantly suppressed tumor growth (n = 3) and metastasis (n = 4) in vivo. When vaccinated before tumor challenge, all mice in vaccine group were tumor-free, whereas all mice in the control group developed tumors within 2 weeks after tumor challenge (n = 10). Cytokine ELISArray revealed elevation of a panel of proinflammatory cytokines in mice receiving LMP1 vaccine. Flow cytometry and interferon-γ ELISPOT assay revealed that LMP1 vaccine induced larger populations of activated CTLs and LMP1-specific T lymphocytes.ConclusionsThis pre-clinical study provides a promising result that LMP1 vaccine suppresses LMP1-expressing tumor growth and metastasis in vivo.

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“…We have previously reported that LMP1 is expressed in most NPC biopsies although its abundance is highly variable. On average, it is much more abundant in NPC biopsies corresponding to the North African juvenile form of the disease [29].…”

Section: Discussionmentioning

confidence: 99%

Polymorphism analysis of Epstein-Barr virus isolates of nasopharyngeal carcinoma biopsies from Tunisian patients

et al. 2007

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Many studies suggest that the focal distribution of nasopharyngeal carcinoma (NPC) may be influenced not only by host genetics, diet and environments but also by interplay with Epstein-Barr virus (EBV) genetics. Specific EBV gene variants (the A and C types, the BamHI f configuration, a C terminal 30 bp deletion and a N terminal loss of an XhoI site in the BNLF1 gene) have been explored in high incidence areas in southern Asian NPC patients. In contrast, in Tunisia where NPC represents the most frequent type of Head and Neck cancer the distribution of these polymorphisms remains poorly investigated. In order to characterize the epidemiology of EBV variants in Tunisian NPC patients, we have investigated the A or B type of the EBV nuclear antigen (EBNA)2 gene, the C or D type of the BamHI W1/I1 region, the F/f variants of the BamHI F region and the presence or the absence of the XhoI site, 30 bp deletion and Taq1 site in the BNLF1 gene in 47 NPC biopsies, 12 being younger than 30 and 35 older than 30. Our results show a unique genetic profile of the tumor EBV strains regarding the A and D types, the prototype F and retention of the XhoI restriction site in the N terminal region of BNLF1 gene. With regard to the C terminal region of this gene, four genetic profiles were detected: (1) the occurrence of the 30 bp deletion in association with the Taq1 site in 39 cases (83%), (2) the presence of the Taq1 site by itself in 5 cases, (3) the occurrence of the 30 bp deletion by itself in 2 cases and (4) the occurrence of a new deletion of 81 bp covering the 30 bp deletion in association with the Taq1 site in one case. With the exception of the 81 bp deletion, which has not been previously described in the literature, the summarized results have shown the same genetic profile in Tunisian NPC tumor isolates as tumor isolates from other North African and Mediterranean countries. Hence, the observed EBV polymorphisms are not fully specific of to the Tunisian NPCs. Nevertheless, the notion of a divergence between North African and Asian tumor EBV isolates is reinforced by this study.

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EBV latent membrane protein 1 abundance correlates with patient age but not with metastatic behavior in north African nasopharyngeal carcinomas

Cited by 63 publications

References 31 publications

Nasopharyngeal carcinoma in Indonesia: epidemiology, incidence,signs, and symptoms at presentation

Nasopharyngeal carcinoma in Indonesia: epidemiology, incidence,signs, and symptoms at presentation

Therapeutic vaccine targeting Epstein-Barr virus latent protein, LMP1, suppresses LMP1-expressing tumor growth and metastasis in vivo

Polymorphism analysis of Epstein-Barr virus isolates of nasopharyngeal carcinoma biopsies from Tunisian patients

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