Evidence of BK Polyomavirus Infection in Urothelial but not Renal Tumors from a Single Center Cohort of Kidney Transplant Recipients.

Cinzia Borgogna,Alessandro Volpe,Silvia Albertini,Guido Merlotti,Marisa Gariglio,Renzo Boldorini,Vicenzo Cantaluppi,Filippo Poletti,Licia Martuscelli

doi:10.3390/v13010056

Abstract

Emerging evidence indicates that reactivation of BK polyomavirus (BKPyV) in the kidney and urothelial tract of kidney transplant recipients (KTRs) may be associated with cancer in these sites. In this retrospective study of a single center cohort of KTRs (n = 1307), 10 clear cell renal cell carcinomas and 5 urinary bladder carcinomas were analyzed from 15 KTRs for the presence of BKPyV infection through immunohistochemistry and fluorescent in situ hybridization (FISH). Three of these patients had already exhibited biopsy-proven polyomavirus-associated nephropathies (PyVAN). Although the presence of BKPyV large-T antigen was evident in the urothelium from a kidney removed soon after PyVAN diagnosis, it was undetectable in all the formalin-fixed and paraffin-embedded (FFPE) blocks obtained from the 10 kidney tumors. By contrast, large-T antigen (LT) labeling of tumor cells was detected in two out of five bladder carcinomas. Lastly, the proportion of BKPyV DNA-FISH-positive bladder carcinoma nuclei was much lower than that of LT-positive cells. Taken together, our findings further strengthen the association between BKPyV reactivation and cancer development in KTRs, especially bladder carcinoma.

Highlights

Immunosuppressive treatment of kidney transplant recipients (KTRs) is a well-known risk factor for infectious diseases and their complications, including infection-related malignancies [1,2,3,4]
DNA genomes of ≈5 kb, divided into three regions: the early region, which encodes the large-T and small-t antigens (LT and sT, respectively); the late region, which encodes the virion structural proteins (VP1, VP2); and the control region, which encompasses the origin of replication and transcription regulatory elements
Emerging evidence indicates that BK polyomavirus (BKPyV) large-T antigen (LT) can promote tumor formation, in part through the upregulation of members belonging to the APOBEC3 family of cytosine deaminases [20]. In this long-term retrospective study of a single center cohort of KTRs, we looked for evidence of human polyomavirus (HPyV) infection in urinary tract and renal tumors by means of immunostaining and fluorescent in situ hybridization (FISH)

Summary

Introduction

Immunosuppressive treatment of kidney transplant recipients (KTRs) is a well-known risk factor for infectious diseases and their complications, including infection-related malignancies [1,2,3,4]. A causal link has been established between the following tumors and viral infections, as examples: (i) anogenital cancer and human papillomavirus (HPV); (ii) Merkel cell carcinoma and Merkel cell polyomavirus (MCPyV); (iii) immune suppression-related non-Hodgkin lymphoma and Epstein–Barr virus (EBV); and (iv) Kaposi’s sarcoma and KS herpesvirus (KSHV/HHV8) [5,6,7,8,9]. A yet to be confirmed association between human polyomavirus (HPyV), especially BK polyomavirus (BKPyV), infection/reactivation with renal (native) or urinary tract (ureter and urinary bladder) carcinoma development has been proposed [5,9,10,11,12,13,14]. Uncontrolled BKPyV infection contributes to polyomavirus-associated nephropathy (PyVAN) in KTRs [15,16,17]

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