COMPLICATIONS - MALIGNANCY

S. Jothy¹, K. Sy¹, V. Iakovlev¹, J.S. Zaltzman^2
1Laboratory Medicine, St. Michael's Hospital, Toronto/CANADA, ²Nephrology/ Transplant, St. Michael's Hospital, Toronto/CANADA

Body: Background: Following organ transplantations, several adverse effects are associated with immunosuppression including a higher risk of developing various cancers. BK polyomavirus re-activation is common after renal transplantation and is known to cause nephropathy and graft failure. However, the possible role of this virus in the etiology of cancer is controversial. We report a 65 year old female patient, who was found to have a urothelial carcinoma in her renal allograft where the tumor was associated with a mutated genotype of BK polyomavirus. Design: The tumor was investigated by histopathology, immunohistochemistry, electron microscopy, PCR amplification of the BK polyomavirus genome, restriction enzyme digestion and DNA sequencing of the amplified fragment. Immunohistochemical studies were performed with a polyomavirus antibody. Polymerase chain reaction of the microdissected tumor was performed with primers specific for the BK polyomavirus and the amplified product was digested with the BamH1 restriction enzyme. The amplified DNA fragment was also sequenced. A PCR fragment isolated from a case of BK nephropathy without associated tumor was used as a control. Result: Following nephrectomy, a 3.8 cm transitional cell carcinoma was found in the pelvis of the renal allograft. Immunohistochemistry showed that all tumor cells were positive for polyomavirus. Electron microscopy showed 42 +/-6 nm viral particles in the nuclei of the tumor cells. PCR of the micro-dissected tumor yielded positivity for the polyomavirus sequence. Unlike the control BK fragment amplified from a non-neoplastic case, the patient's BK fragment could not be cut by the BamH1 restriction enzyme. DNA sequencing of the PCR product showed a mutation in the BK polyoma viral genome: GGATTC instead of the wild type GGATCC sequence, in agreement with the result of the BamH1 restriction enzyme analysis.Conclusion: Our results indicate that the BK polyomavirus may be present within tumor cells of urothelial carcinoma developing inallografted kidney, and might participate in this particular form of tumorigenesis. This report is the first demonstration of an association between a mutated form of BK polyoma virus and a humanmalignant tumor, including a tumor arising in a renal allograft.

Disclosure: All authors have declared no conflicts of interest.