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Review
.2017 Aug;53(3):95-109.
doi: 10.1016/j.jdsr.2017.01.002. Epub 2017 Mar 15.

Epstein-Barr virus (EBV)-associated epithelial and non-epithelial lesions of the oral cavity

Affiliations
Review

Epstein-Barr virus (EBV)-associated epithelial and non-epithelial lesions of the oral cavity

Kentaro Kikuchi et al. Jpn Dent Sci Rev.2017 Aug.

Abstract

Epstein-Barr virus (EBV) is known to be associated with the development of malignant lymphoma and lymphoproliferative disorders (LPDs) in immunocompromised patients. EBV, a B-lymphotropic gamma-herpesvirus, causes infectious mononucleosis and oral hairy leukoplakia, as well as various pathological types of lymphoid malignancy. Furthermore, EBV is associated with epithelial malignancies such as nasopharyngeal carcinoma (NPC), salivary gland tumor, gastric carcinoma and breast carcinoma. In terms of oral disease, there have been several reports of EBV-related oral squamous cell carcinoma (OSCC) worldwide. However, the role of EBV in tumorigenesis of human oral epithelial or lymphoid tissue is unclear. This review summarizes EBV-related epithelial and non-epithelial tumors or tumor-like lesions of the oral cavity. In addition, we describe EBV latent genes and their expression in normal epithelium, inflamed gingiva, epithelial dysplasia and SCC, as well as considering LPDs (MTX- and age-related) and DLBCLs of the oral cavity.

Keywords: Activation-induced cytidine deaminase (AID); Early growth transcription response-1 (Egr-1); Epstein–Barr virus (EBV); MTX- and age-related EBV + B-cell LPD; Oral squamous cell carcinoma (OSCC).

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Figures

Figure 1
Figure 1
Human tumor associated EBV is related to a wide range of human epithelial and non-epithelial malignancies.
Figure 2
Figure 2
Detection of theEBNA-2 genes in oral squamous cell carcinomas (OSCCs) by PCR. PCR analysis of Epstein–Barr virus (EBV) genes in formalin-fixed, paraffin-embedded tissues. The detection rate ofEBNA-2 (206 bp) in OSCC specimens was 52.0%. Positive and negative cases are marked red and green, respectively.EBNA-2 bands showed the same level as those in Raji cells used as a positive control.
Figure 3
Figure 3
EBER and LMP-1 expression in OSCCs detected by ISH and IHC. HE staining (a, d), EBER (b, e), and LMP-1 (c, f). Positive reaction for EBER and LMP-1 shows a similar distribution in OSCC (b, c). Reaction for EBER is weakly positive in SCC, and inflammatory cells are strongly positive in the stroma (e). Reaction for LMP-1 is strongly positive in SCC and inflammatory cells in the stroma (f). (a–c, original magnification, ×12.5, d–f, original magnification, ×200).
Figure 4
Figure 4
Expression of LMP-1 in gingivitis, epithelial dysplasia and OSCC. LMP-1 expression was greater in severe epithelial dysplasia than in inflamed gingiva, mild to moderate epithelial dysplasia and OSCC.P values were determined by Mann–WhitneyU test (*P < 0.05,**P < 0.01).
Figure 5
Figure 5
Intractable mucosal ulcers or healing failure of extraction sockets. Buccal ulcer (a) and ongue ulcer (b) in rheumatoid arthritis patients treated with MTX. Failure of gingival mucosa (c) and bone (d) healing in a senile patient after tooth extraction .
Figure 6
Figure 6
Normal expression of AID in lymphoid tissue. HE staining (a), AID (b). Normal expression of AID is evident in germinal centers of lymph nodes with reactive lymphoid hyperplasia. (a, b, original magnification, ×100).
Figure 7
Figure 7
Distribution and intensity of AID expression in biopsy specimens of MTX-/age-related EBV-LPDs and DLBCLs. HE stain (a–c), and AID (d–f) detected by IHC (brownish color). AID-positive atypical lymphoid cells show diffuse in MTX-LPD (d) and age-related LPD (e), but are few in DLBCL (f). AID positive cells show strong intensity in MTX-LPD (d) and Age-related LPD (e), and weak or moderate intensity in DLBCL (f). (a–f, original magnification, ×200).
Figure 8
Figure 8
A recentin vitro study by Kim et al. has shown that LMP-1 increases genomic instability through Egr-1-mediated upregulation of AID in B-cell lymphoma cell lines. A recentin vivo study has demonstrated overexpression of AID, including LMP-1 and Egr-1, in LPDs (MTX- and age- related) associated with pre-cancerous states due to immunosuppression in the head and neck. In LPDs that occur in patients who are immunosuppressed due to MTX administration or ageing, memory B-cells without mutation/translocation first express LMP-1 by reactivation of EBV latent genes. Secondly, LPDs with polyclonal growth show an increase AID expression through the LMP-1/NF-kB/Egr-1 signaling pathway, and LPDs with monoclonal proliferation undergo gene mutation or gene translocation throuugh the effect of increased AID. Abnormal long-term expression of AID in LPDs leads to development of true malignant lymphoma, and the changed malignant B-cell lymphomas show an increase of AID expression through acquired monoclonal growth. On the other hand, lymphoma caused by a gene mutation will develop when the expression of AID is absent or low involved.
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References

    1. Epstein M.A., Achong B.G., Barr Y.M. Virus particles in cultured lymphoblasts from Burkitt’s lymphoma. Lancet. 1964;1:702–703. - PubMed
    1. Okano M., Gross T.G. Advanced therapeutic and prophylactic strategies for Epstein–Barr virus infection in immunocompromised patients. Expert Rev Anti Infect Ther. 2007;5:403–413. - PubMed
    1. Shimizu N., Tanabe-Tochikura A., Kuroiwa Y., Takada K. Isolation of Epstein–Barr virus (EBV)-negative cell clones from the EBV-positive Burkitt’s lymphoma (BL) line Akata: malignant phenotypes of BL cells are dependent on EBV. J Virol. 1994;68:6069–6073. - PMC - PubMed
    1. Yates J.L., Warren N., Sugden B. Stable replication of plasmids derived from Epstein–Barr virus in various mammalian cells. Nature. 1985;313:812–815. - PubMed
    1. Shirakata M., Imadome K.I., Hirai K. Requirement of replication licensing for the dyad symmetry element-dependent replication of the Epstein–Barr virus oriP minichromosome. Virology. 1999;263:42–54. - PubMed

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