Epstein‐barr virus carriage by nasopharyngeal carcinoma in situ

Abstract

We studied the distribution of the EBV genome in tumour biopsies obtained from 42 patients with poorly differentiated or undifferentiated nasopharyngeal carcinoma (NPC) and 3 patients with well-differentiated NPC. Six carcinoma in situ (CIS) foci were seen in 5 tumour specimens. By in-situ hybridization, multiple copies of the EBV genome were detected in some of the tumour cells in 3 CIS lesions involving the full thickness of the mucosal epithelium, but without microinvasion, while the viral genome was present in the majority of the tumour cells contained in another 3 CIS lesions with microinvasion. In agreement with previous findings, poorly differentiated and undifferentiated carcinomas regularly carried the viral genome, the number of copies of which was similar to that seen in CIS, while some, but not all, of the tumour cells of the well-differentiated histological type carried the virus. The viral genome was otherwise rarely detected in other areas of the mucosal epithelium and, where present, the viral carriage was confined to a few epithelial cells, in which the viral genome contents were markedly lower than in tumour cells. These results suggest that EBV may first become associated with NPC at an early stage of the disease shortly after the tumour has been initiated.

An Update on Epstein-Barr Virus and Nasopharyngeal Carcinogenesis

“…As invasive NPC, nasopharyngeal carcinoma insitu is positive for EBV (EBER) (Fig. 2), a finding that supports the concept that EBV infection in an early event in NPC carcinogenesis [10,17,18]. The absence of EBV-infected epithelial cells in normal nasopharyngeal mucosa from individuals at high risk of developing NPC argues against a pre-existing normal reservoir infected cells from which virus-positive carcinoma arise; however, deletions in chromosome regions 3p and 9p have been identified in low-grade dysplastic lesions and normal nasopharyngeal mucosa of individuals at high risk of developing NPC indicating that these genetic events occur early in the pathogenesis of NPC and that they might cause predisposition to subsequent EBV infection [19,20].…”

“…Although NPC in-situ can be identified in approximately less than 10% of conventional invasive NPC, pure nasopharyngeal carcinoma in-situ is exceedingly rare [10,17,18]. As invasive NPC, nasopharyngeal carcinoma insitu is positive for EBV (EBER) (Fig.…”

“…Inactivation of the RASSF1A and p16 tumor suppressor genes on 3p21 and 9p21 by homozygous deletions and promoter methylation are the most common alterations described in NPC [30][31][32]. 3p and 9p abnormalities have been identified in low-grade dysplastic lesions and normal nasopharyngeal mucosa of individuals at high risk indicating that these genetic changes are early events in the pathogenesis of NPC [10,17,20,33]. Other genes frequently inactivated by promoter methylation in NPC include TSCL1 at 11q23 and EDNRB at 13q22, E-cadherin, and death-associated protein kinase (DAPK) [34][35][36].…”

The Enigmatic Epidemiology of Nasopharyngeal Carcinoma

“…Because the EBV episome is identical in every tumor cell-as assessed by the number of terminal repeats in the latent, circularized form of the virus in NPC tumors (106, 107, 110-112)-NPC may originate from a single progenitor cell infected with EBV before clonal expansion. Clonal EBV has also been detected in severe dysplasia or carcinoma in situ of the nasopharynx (113,114), indicating a role for the virus in the early stages of tumor progression.…”

The prognostic value of IgA/[EBNA1+VCA-p18] on survival of nasopharyngeal cancer patients

“…More than 90% of NPC in Indonesia comprised of histology type World Health Organization (WHO) III or undifferentiated carcinoma which is strongly correlated with Epstein-barr virus (EBV) infection (Soeripto, 1997;Adham et al, 2012). Consistent expression of EBV gene products in nasopharyngeal cancer cells, specific immune response to EBV antigen in NPC patients, as well as detection of EBV in premalignant lesion support the pathogenic role of EBV in NPC (Henle et al,1970;Wolf et al, 1973;Henle, 1976;Ho et al, 1976;Zeng et al 1982Zeng et al , 1983Yeung et al, 1993;Sam et al, 1994;Pathmanathan et al, 1995;Gulley, 2001;Chien et al, 2001;Middeldorp et al, 2003). Although NPC is sensitive to radiotherapy and chemotherapy, recurrence rate of NPC during the first 2-year post treatment remains high (2-year progression free survival is less than 53% with median time to progression is 17.4 month) in our centre (Taroeno-Hariadi et al, 2005 unpublished observation).…”