In situ Detection of Epstein-Barr Virus Markers in Nasopharyngeal Carcinoma Patients

Lung, Maria Li; Chan, Kwok Hung; Lam, Wai Pang; Kou, Sio Kei; Choy, D.; Chan, C. W.; Ng, Mun Hon

doi:10.1159/000226739

Cited by 34 publications

(16 citation statements)

References 8 publications

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“…In situ studies have shown the presence of EBV in car cinoma, and dysplastic epithelia of the nasopharynx [27,30,31], and occasionally in normal epithelium of NPC [9,31]. In this study, we were able to demonstrate EBER 1 in the squamous epithelia in NPC cases but not in the respi ratory epithelial cells.…”

Section: Discussionsupporting

confidence: 50%

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Differential Expression of EBER1 in Nontumor Nasopharyngeal Biopsies and Nontumor Component of Nasopharyngeal Carcinoma

Chen¹,

Hsu

Hsu³

1996

Intervirology

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The close association of Epstein-Barr virus (EBV) and nasopharyngeal carcinoma (NPC) is well documented and the expression of EBV-related latent genes has been shown in NPC. Nevertheless, the status of EBV infection in the nontumor epithelial and lymphoid cells is not known. In this study, we detected EBV in the nontumor component of NPC and nontumor nasopharyngeal biopsies by in situ hybridization using digoxigenin-labeled antisense EBER1 oligoprobe in 346 nasopharyngeal biopsies. Latent membrane protein (LMP) and ZEBRA were detected by immunohistochemistry in cases containing EBER1-positive cells. The EBV-positive epithelial and lymphoid cells were identified by immunostains for cytokeratin and lymphoid phenotypes. In the nontumor nasopharyngeal biopsies, 21 (11.7%) of 179 cases had EBV-harboring lymphocytes in the lymphoid tissue, while the overlying mucosa was all negative. LMP was demonstrated in lymphoid cells of 14 (66.7%) of these 21 samples. These EBV-positive lyphocytes were B lymphocytes by combined phenotype study. EBER1-containing metaplastic squamous cells were demonstrated in the overlying mucosa close to the tumor tissue in 14 (8.4%) of 167 NPC samples. In contrast, the respiratory epithelial cells in these cases were all negative. Two (1.2%) of these cases had EBV-positive lymphocytes in the lymphoid stroma. Four of the 346 cases had ZEBRA-positive cells. This study demonstrated that latent infection and, occasionally, active replication of EBV were present in stromal B lymphocytes in nasopharyngeal tissue with and without NPC. EBER1 was found only in the metaplastic squamous cells in the mucosa of nasopharyngeal tissues with NPC, but not in those without NPC.

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Section: Discussionsupporting

confidence: 50%

“…Several studies have shown that EBV-harboring epithelial cells are occasionally present in the overlying mucosa of NPC [4,9], Little is known about persistent EBV infec tion in normal or nontumor nasopharyngeal mucosa and lymphoid cells.…”

Section: Introductionmentioning

confidence: 99%

Differential Expression of EBER1 in Nontumor Nasopharyngeal Biopsies and Nontumor Component of Nasopharyngeal Carcinoma

Chen¹,

Hsu

Hsu³

1996

Intervirology

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“…Several studies have pointed out that human papillomavirus infection is associated with increased risk of oral cancer, independent of exposure to tobacco and alcohol (35,36). Therefore, up-regulations of ISGs, including IFIT2, at the tumor site could be caused by IFNs produced in response to ongoing viral replication in adjacent tissue, as reported for nasopharyngeal carcinoma patients with EBV infection (37). Whether the enhanced expression of IFIT2 in OSCC tissues is due to the inflammatory response to viral infection or chemicals warrants further investigations.…”

Section: Discussionmentioning

confidence: 93%

IFN-Induced Protein with Tetratricopeptide Repeats 2 Inhibits Migration Activity and Increases Survival of Oral Squamous Cell Carcinoma

Lai

Chang²,

Liu

et al. 2008

Molecular Cancer Research

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The function of the IFN-stimulated gene family protein, IFN-induced protein with tetratricopeptide repeats 2 (IFIT2), is poorly understood. Here, we report that IFIT2 colocalizes with cytokeratin 18 in oral squamous cell carcinoma (OSCC) cells. Treatment of OSCC cells with IFN-B significantly increased the expression of IFIT2 and remarkably inhibited cell migration. To further explore the effect of IFIT2 on cell migration, IFIT2 expression was either silenced with a small interfering RNA or increased by ectopic expression. IFIT2 knockdown in OSCC cells led to a significantly higher level of migration in vitro (P < 0.05) compared with control cells; by contrast, IFIT2 overexpression led to a significantly lower level of migration in vitro (P < 0.05). Immunohistochemically, 71.4% of OSCC tissues had elevated IFIT2 protein levels compared with noncancerous matched tissues. Elevated IFIT2 protein expression was positively associated with tumor differentiation status and inversely associated with nodal stage in OSCC specimens (P < 0.05). Higher IFIT2 protein levels in tumor tissues were also associated with better patient survival (P < 0.01). Our present study shows an inverse correlation between IFIT2 expression and cell migration, suggesting that IFIT2 plays an important role in inhibiting this process and that its expression may be associated with better prognosis in patients with OSCC.

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“…There is precedence for this in studies with varicella zoster that showed IFN production not in the infected cells per se but in the adjacent uninfected cells, thereby creating an antiviral state around the site of viral replication that functions to impede the spread of the virus to adjacent tissue (44). The up-regulation of ISGs at the tumor site could also be caused by IFNs produced in response to ongoing viral replication in tissue adjacent to the tumor (45). This would be consistent with serologic studies, which indicate that increasing levels of IgA antibodies to replicative antigens are diagnostic of NPC disease progression and relapse (46), although there is little viral replication in the tumor itself.…”

Section: Cancer Researchmentioning

confidence: 99%

IFN-α–Stimulated Genes and Epstein-Barr Virus Gene Expression Distinguish WHO Type II and III Nasopharyngeal Carcinomas

et al. 2007

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Nonkeratinizing nasopharyngeal carcinoma (NPC) is 100% associated with Epstein-Barr Virus (EBV) and divided into two subtypes (WHO types II and III) based on histology. We tested whether these subtypes can be distinguished at the molecular genetic level using an algorithm that analyzes sets of related genes (gene set enrichment analysis). We found that a class of IFN-stimulated genes (ISG), frequently associated with the antiviral response, was significantly activated in type III versus type II NPC. Consistent with this, replication of the endogenous EBV was suppressed in type III. A strong association was also seen with a subset of ISGs previously identified in systemic lupus erythematosus, another disease in which 'normal' EBV biology is deregulated, suggesting that this pattern of ISG expression may be linked to the increased EBV activity in both diseases. In contrast, unsupervised hierarchical clustering of the complete expression profiles failed to distinguish the two subsets. These results suggest that type II and III NPC have not originated from obviously distinct epithelial precursors; rather, the histologic differences may be a consequence of a differential antiviral response, involving IFNs, to chronic EBV infection. [Cancer Res 2007;67(2):474-81]

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In situ Detection of Epstein-Barr Virus Markers in Nasopharyngeal Carcinoma Patients

Cited by 34 publications

References 8 publications

Differential Expression of EBER1 in Nontumor Nasopharyngeal Biopsies and Nontumor Component of Nasopharyngeal Carcinoma

Differential Expression of EBER1 in Nontumor Nasopharyngeal Biopsies and Nontumor Component of Nasopharyngeal Carcinoma

IFN-Induced Protein with Tetratricopeptide Repeats 2 Inhibits Migration Activity and Increases Survival of Oral Squamous Cell Carcinoma

IFN-α–Stimulated Genes and Epstein-Barr Virus Gene Expression Distinguish WHO Type II and III Nasopharyngeal Carcinomas

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