JC virus T-antigen expression in sporadic adenomatous polyps of the colon

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.