Significance of p53 Expression and Tubulo-Interstitial Inflammation in Renal Transplant with BK Virus Nephropathy.
Ryuji Ohashi, Darshana Dadhania, Manikkam Suthanthiran, Surya V Seshan. Weill Cornell Medical Center, New York, NY; Nippon Medical School, Tokyo, Japan
Background: P53 expression has been localized in BKV positive nuclei, but its significance remains obscure in BK virus nephropathy (BKVN). We assessed p53 expression in renal tubular nuclei in BKVN renal tranplant biopsies (TrBx) and its association with other histological parameters.
Design: Tubular expression of p53 and BK virus was immunohistochemically quantified in renal TrBx with BKVN (n=31) in serial sections. Morphological features including viral cytopathic changes (vcc), interstitial inflammation (i), tubulitis (t), interstitial fibrosis (ci) and tubular atrophy (ct) were scored as; 0-3. The frequency of interstitial inflammatory cell types (polymorphonuclear leukocytes PMN, plasma cells PC, and CD3+ and CD20+ lymphocytes) were scored as 0-3. 15 cases with an increase in creatinine of more than 0.5 mg/dl after BKVN diagnosis were classified as decline in function group (BKVN-DF) and the remaining 16 BKVN without an increase in creatinine were classified as stable function group (BKVN-SF). As control BKV – TrBx, acute tubular injury (ATI), acute cellular rejection (ACR), acute antibody mediated rejection and interstitial fibrosis and tubular atrophy, were used and stained for tubular p53.
Results: In BKVN, p53 co-localized with BKV within tubular nuclei showing intranuclear inclusions and hyperchromasia. P53 expression was higher in BKVN than BKV – control cases (p<0.05), the latter showing p53 in tubules with injury and regenerative changes (ATI) or tubulitis (ACR). In BKVN, although there was proportional correlation between the numbers of p53+ and BKV+ cells (r=0.72, p<0.05), the total p53+ cell number was higher than BKV+ cells in cases with moderate to severe inflammation (i2, i3, t2, t3)(P<0.05). In cases with higher grades (2-3) of PMN, PC and CD3+ inflammatory infiltrates, the p53+ cells were also more than BKV+ cells (p<0.01). In BKVN-DF group, the total p53+ cell number was significantly higher than BKVN-SF (7.8±4.7/HPF vs 4.8±3.0, p<0.05) while BKV+ cells showed no significant difference (p = 0.7).
Conclusions: In BKVN, co-localization of p53 and BKV indicates a direct link between p53 and BKV infection within tubular nuclei. Increased p53+ cells in cases with significant inflammation may suggest augmented p53 expression by accompanying active interstitial inflammation. The increased ratio of tubular p53+ to BKV+ cells in BKVN may serve as a potential prognostic histologic marker.
Category: Kidney (does not include tumors)
Wednesday, March 2, 2011 1:00 PM
Poster Session VI # 272, Wednesday Afternoon