@article{mbs:/content/journal/jgv/10.1099/vir.0.19217-0, author = "zur Hausen, Axel and van Beek, Josine and Bloemena, Elisabeth and ten Kate, Fiebo J. and Meijer, Chris J. L. M. and van den Brule, Adriaan J. C.", title = "No role for Epstein–Barr virus in Dutch hepatocellular carcinoma: a study at the DNA, RNA and protein levels", journal= "Journal of General Virology", year = "2003", volume = "84", number = "7", pages = "1863-1869", doi = "https://doi.org/10.1099/vir.0.19217-0", url = "https://www.microbiologyresearch.org/content/journal/jgv/10.1099/vir.0.19217-0", publisher = "Microbiology Society", issn = "1465-2099", type = "Journal Article", abstract = "Epstein–Barr virus (EBV) has been suggested to play a role in hepatocellular carcinoma (HCC). However, reports on detailed EBV transcript analyses in HCCs are limited. It was shown recently that expression of the transforming BARF1 (BamHI A rightward open reading frame 1) gene of EBV is restricted to latently EBV-infected epithelial malignancies, i.e. nasopharyngeal carcinoma and gastric carcinoma. The aim of this study was to test the presence of EBV in Dutch HCCs. A semiquantitative DNA PCR-enzyme immunoassay (PCR-EIA) for the BamHI W fragment of EBV was used to assess the presence of EBV in frozen and paraffin-embedded tissues of 16 HCCs. In addition, several RNA detection techniques, i.e. nucleic acid sequence-based amplification (NASBA), RT-PCR, RNA in situ hybridization (RISH) and immunohistochemistry (IHC), were applied. Five of 16 HCCs and two of four hepatitis C virus hepatitis samples were weakly positive for EBV DNA by PCR-EIA. Using sensitive RNA transcription techniques, no transcripts were found for BARF1, EBNA-1 and BARTs (BamHI A rightward transcripts) in any of the liver tissues tested. In addition, RISH for EBER1/2 and BARTs and IHC for EBNA-1, LMP-1 and ZEBRA, performed on the paraffin-embedded tissue of the PCR-EIA-positive cases and on adjacent non-neoplastic liver tissues, were negative. The absence of epithelial-specific BARF1 transcripts and other EBV transcripts and proteins in the EBV DNA PCR-positive cases argues strongly against a role for EBV in HCC.", }