Epstein-Barr virus expression within keratinizing nasopharyngeal carcinoma

Abstract

Three stages of maturation can be seen in keratinizing nasopharyngeal carcinomas. These stages are similar morphologically to basal cells, intermediate and superficial squamous cells seen in normal squamous epithelium. Taking advantage of such a diverse tumour cell population, 10 keratinizing nasopharyngeal carcinoma (NPC) were examined by in situ hybridization for the presence of latent Epstein-Barr Virus (EBV) using EBV encoded RNAs (EBERs) and by immunohistology for the presence of EBV early antigen-diffuse (EA-D) and the 350/220 kd membrane glycoprotein of the EBV. The basal cell-like tumour cells are mainly infected latently with the virus; viral replication was found in isolated intermediate squamous cells, whilst superficial squamous cells are largely depleted of all the viral markers. We used a control series of nonkeratinizing nasopharyngeal carcinomas composed of undifferentiated and poorly differentiated tumour cells and EBV latency was present in these tumours. Viral replication was detected by RT-PCR, in the undifferentiated tumours but viral replication was not seen by immunohistology. The possible relationship between EBV life cycle in these tumours and tumour cell differentiation is discussed in the light of these findings.

Diagnostic Value of Measuring Epstein-Barr Virus (EBV) DNA Load and Carcinoma-Specific Viral mRNA in Relation to Anti-EBV Immunoglobulin A (IgA) and IgG Antibody Levels in Blood of Nasopharyngeal Carcinoma Patients from Indonesia

“…This phenomenon may relate to de novo B-cell infection due to local lytic viral replication in NPC (16,61,68), of which IgG and IgA reactivity to numerous early and late lytic viral antigens in NPC patients is a reflection (15). An enhanced replication frequency of circulating EBV-positive B cells may lead to higher levels of EBNA1 mRNA expression (14,23).…”

“…During the period from 2001 to 2003, 149 NPC patients were identified at the Department of Pathology, Gadjah Mada University, School of Medicine/Sardjito Academic Hospital (Yogyakarta, Indonesia). NPC diagnosis was based on pathological assessment of paraffin-embedded tumor biopsy specimens, EBER1/2 RNA in situ hybridization, and immunohistochemical staining for EBNA1 and LMP1 by using previously defined monoclonal antibodies (35,36,68). TNM staging for tumor size (T), lymph node involvement (N), and metastasis (M) was done by using the 1997 criteria of the Union International Contre le Cancer (49) for all patients by using clinical measurements and computer tomography scans as part of the routine patient workup.…”

Hypothesis: a novel route for immortalization of epithelial cells by Epstein-Barr virus

“…If one hypothesizes that an EBV protein might bind DNA near or at telomere sites and prevent their shortening, the question would be which of the viral proteins, within p31 DNA, might ful®l this role? Candidate genes may be found among those associated with the epithelial cell tumours, such as NPC (Hitt et al, 1989;Chen et al, 1992;Brink et al, 1998;Zhang et al, 1998;Hayes et al, 1999;Xue et al, 2000;Smith et al, 2000), see Figure 1. There is no suggestion in the literature (Strockbine et al, 1998) or in its structure (Baer et al, 1984), that BARF1, the only p31-containing viral function known to stimulate cell growth (Wei and Ooka, 1989;Wei et al, 1994Wei et al, , 1997, might act in this manner.…”

Adoptive transfer of autologous Epstein-Barr virus-specific cytotoxic T cells for nasopharyngeal carcinoma

“…However, the viral genome detected in the PBMC samples probably originated in latently infected resting B cells. With viral expression being confined to EBER and LMP2A, 43,44,51,52 these cells are presented as weak T-cell targets and evidently enabled the latently infected B cells to escape from host immune surveillance. Consequently, the EBV burden borne by PBMCs was not correlated with CTLp level or plasma EBV burden.…”