Association of Epstein-Barr virus with oral cancers
ABSTRACT Epstein-Barr virus (EBV) persists in the epithelial cells of oral mucosa and often replicates on them. EBV is known to be a causative agent of nasopharyngeal carcinoma. We suspect that EBV may be associated with oral cancers, and thus examined EBV expression on 28 tongues and 9 other oral cancers. We also examined 6 metastatic lesions in the lymph nodes. All cancers were squamous cell carcinoma (SCC). We used mRNA in situ hybridization, immunofluorescence staining, reverse transcriptase-polymerase chain reaction (RT-PCR), and polymerase chain reaction (PCR). The mRNA in situ hybridization using a probe comprising the transcripts of the BamHIW fragment of the EBV genome demonstrated EBV mRNA in the majority of tumor cells in all cases of oral cancer, but in none of the normal tissues. RNA in situ hybridization using an EBER1 probe detected RNAs in 16 out of 24 cancers. Also, mRNA in situ hybridization using a probe of the EBV-determined nuclear antigen-2 (EBNA2) region detected positive signals in 9 out of 12 cancers. Furthermore, EBNA2, latent membrane protein-1 (LMP1) and BZLF1 were detected in these cancers by immunofluorescence staining, but were not detected in any of the epithelial cells of the normal tissues. Four out of 6 metastatic tissues showed stronger fluorescence than that in the primary tissues. RT-PCR analysis also showed EBER1 expression in 1 of the 3 tongue cancers. PCR detected the BamHIW sequence of EBV DNA in all cases, including the normal tissues tested. These findings indicate that EBV may be involved in neoplastic transformation in oral cancers, such as nasopharyngeal carcinoma.
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ABSTRACT: Background: The aim of this study was to determine the prevalence and viral load of Epstein–Barr virus (EBV) and Human herpesvirus-6 (HHV-6) in different histopathologic grades of oral squamous cell carcinoma (OSCC). Methods: Forty-five formalin-fixed paraffin-embedded tissue section of OSCC patients were analyzed by quantitative real-time polymerase chain reaction for detection of EBV and HHV-6. Results: The mean age of the patients was 58.6 years, 69% of whom were female, and 31% were male. Overall, the positive rate for EBV and HHV-6 were 16.7% and 27.1%, respectively; and the mean viral load EBV was 27.9 × 103 and 38.5 × 103 for HHV-6. No correlation was demonstrated between the viral load of EBV DNA (P = 0.35) and HHV-6 (P = 0.38) at the different OSCC histopathologic grades. Conclusions: These findings neither lend support to the hypothesis that EBV and HHV-6 are directly involved in OSCC nor rule out the possibility that these viruses play an indirect role in carcinogenesis in this area.International journal of preventive medicine 10/2014; 5(10):1231-1238.
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ABSTRACT: Occurrence of genetic and epigenetic alterations affecting p14ARF and p16INK4A were investigated in tumour samples of 37 oral (OSCC) and 28 laryngeal squamous cell cancer (LSCC) patients, and compared to exfoliated buccal epithelial cells of 68 healthy controls. Presence of deletions and mutations/polymorphisms affecting exons were examined using sequencing. Methylation status of promoters was assessed by methylation-specific PCR. Chi-square and Fisher's exact tests were used to compare frequency of events. Exon deletions were found in four controls, one OSCC and 22 LSCC patients; the latter significantly differed from controls (p < 0.001). Only two mutations (T24610A and C24702A) were in p16 exon 1 of two OSCC patients. Polymorphisms G28575A (Ala140Thr), G31292C (C540G) and G28608A were found in both patient groups. The p14 promoter was unmethylated in 86.7 % of OSCC and in 85.7 % of LSCC patients; for the p16 promoter these rates were 69.0 % and 76.2 % for OSCC and LSCC patients, respectively. Combining the two patient groups, unmethylated promoter was significantly less frequent in case of both p14 and p16 (p = 0.043 and p = 0.001, respectively) compared to the control group. In summary, exon deletion may be important in LSCC, while promoter methylation was relatively frequent in both patient groups.Pathology & Oncology Research 04/2014; 20(4). DOI:10.1007/s12253-014-9775-9 · 1.81 Impact Factor
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ABSTRACT: Epstein-Barr virus (EBV) is a ubiquitous pathogen that was first identified as a human cancer virus. Many human cancers are associated with EBV, and we demonstrated that EBV infects macrophages. Macrophages infected with EBV show a close correlation with many human cancers, and thus more attention must be given to the role of macrophages infiltrating into cancer tissues associated with EBV. In this review, I discuss the role of macrophages in the process of EBV-associated oncogenesis with regard to interleukin-10.Oncology Reports 09/2014; 32(5). DOI:10.3892/or.2014.3475 · 2.19 Impact Factor