Abstract
BACKGROUND: JC virus (JCV) has been implicated in the pathogenesis of colorectal cancer; however, its role in premalignant lesions is unknown. The hypothesis that JCV DNA sequences and T-antigen (T-Ag) expression may be present in adenomatous polyps of the colon was tested. Furthermore, an association between JCV and microsatellite instability (MSI) was also sought in these lesions. METHODS: DNA was extracted from 74 paraffin-embedded adenomatous polyps. JCV gene sequences were amplified by polymerase chain reaction (PCR), and the specificity confirmed by DNA sequencing. Immunohistochemical staining was performed to localize T-Ag expression in the adenomas using a monoclonal antibody. For microsatellite instability analysis, 5 mononucleotide repeat markers (BAT-25, BAT-26, NR-21, NR-24, and NR-27) were coamplified in a pentaplex PCR and analyzed for deletion mutations. RESULTS: JCV T-Ag sequences were found in 82% (61 of 74) of adenomas, and T-Ag protein was expressed in 16% (12 of 74) of these polyps. The T-Ag staining was localized exclusively in the nuclei of adenoma cells, but never in the cytoplasm or the adjacent nonneoplastic cells. The prevalence of MSI-H and non-MSI-H (MSI-L/MSS) in adenomatous polyps was 9.5% (7 of 74) and 90.5% (67 of 74), respectively. Among the 61 adenomas that harbored JCV sequences, 8% (5 of 61) were MSI-H, and similarly among 12 adenomatous polyps expressing T-Ag protein 8% (1 of 12) of the adenomatous polyps were MSI-H. CONCLUSIONS: JCV T-Ag DNA sequences are frequently present in adenomatous polyps of the colon, and T-Ag is expressed specifically in the nuclei of these premalignant lesions. This study indicates that JCV T-Ag is present in the early stage of colonic carcinogenesis. Future studies will be required to determine the molecular mechanism of carcinogenesis in these JCV-infected lesions.