Adjuvant role of p53 immunostaining in detecting BK viral infection in renal allograft biopsies.

BK virus infection is a significant threat to renal transplant outcome. Detecting viral infection in renal transplant biopsies using SV40 staining is less than ideal. SV40 antibody reacts with the large T-antigen of BK virus only at the early phases of infection and can miss cells in later stages of infection. As p53 is upregulated during both early and late phases of infection, this study set out to determine whether p53 staining could improve detection of BK virus infection in renal transplant patients. The control group consisted of 16 renal allograft biopsies without histologic evidence of BK virus infection, while the BK group consisted of 15 renal allograft biopsies with histologic evidence of BK virus infection. The biopsies from both groups were immunohistochemically stained with both SV40 and p53 antibodies. Dual staining with both markers was also performed to identify their nuclear co-localization. In the BK group, the percent of p53 staining (16.6 ± 4.8 %) was significantly higher than the percent of SV40 staining (5.4 ± 2.7%). BK virus infected cells revealed a unique p53 immunostaining pattern (strong nuclear staining with a central halo). Co-localization of SV40 and p53 was identified in cells that had characteristic nuclear features of BK virus infection by histology. The sensitivity and specificity for using p53 staining to identify BK infected cells was 92% and 86 %, respectively. In conclusion, p53 staining detects a higher percentage of BK virus infected cells than SV40 staining alone. Thus, for diagnosis of BK virus infection in renal allograft biopsies, p53 staining is a sensitive and specific method when used along with SV40 staining.

[1]  J. Gralla,et al.  Aggressive immunosuppression minimization reduces graft loss following diagnosis of BK virus-associated nephropathy: a comparison of two reduction strategies. , 2008, Clinical journal of the American Society of Nephrology : CJASN.

[2]  F. Gudat,et al.  BK virus large T and VP-1 expression in infected human renal allografts , 2008, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[3]  J. Krzesinski,et al.  Polyomavirus in Renal Transplantation: A Hot Problem , 2008, Transplantation.

[4]  A. Chang,et al.  Nephron segment localization of polyoma virus large T antigen in renal allografts. , 2006, Human pathology.

[5]  T. Larson,et al.  Kidney Transplant Function and Histological Clearance of Virus Following Diagnosis of Polyomavirus‐Associated Nephropathy (PVAN) , 2006, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[6]  J. Jordan,et al.  Treatment of Renal Allograft Polyoma BK Virus Infection with Leflunomide , 2006, Transplantation.

[7]  J. Papadimitriou,et al.  Polyomavirus disease in renal transplantation: review of pathological findings and diagnostic methods. , 2005, Human pathology.

[8]  M. Suthanthiran,et al.  Polyomavirus-Associated Nephropathy in Renal Transplantation: Interdisciplinary Analyses and Recommendations , 2005, Transplantation.

[9]  J. Papadimitriou,et al.  Histological Patterns of Polyomavirus Nephropathy: Correlation with Graft Outcome and Viral Load , 2004, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[10]  G. Herrera,et al.  P53 Protein Is a Reliable Marker in Identification of Renal Tubular Injury , 2004, Applied immunohistochemistry & molecular morphology : AIMM.

[11]  M. Imperiale,et al.  BKV and SV40 infection of human kidney tubular epithelial cells in vitro. , 2004, Virology.

[12]  Shivakumar Cv,et al.  Interaction of human polyomavirus BK with the tumor-suppressor protein p53. , 1996 .

[13]  M. Imperiale,et al.  BK virus large T antigen: interactions with the retinoblastoma family of tumor suppressor proteins and effects on cellular growth control , 1996, Journal of virology.

[14]  C. Smith,et al.  Prospective study of the human polyomaviruses BK and JC and cytomegalovirus in renal transplant recipients. , 1984, Journal of clinical pathology.