Expression of p16/INK4a in posttransplantation lymphoproliferative disorders

It was recently demonstrated that classification of posttransplantation lym phoproliferative disorders (PT-LPDs) into morphological and molecular categ ories is clinically relevant. It was also reported that PT-LPD not associat ed with Epstein-Barr virus (EBV) had a more aggressive course than most les ions associated with EBV, Because the cyclin-dependent kinase inhibitor p16 /INK4a has been reported to be frequently inactivated in high-grade lymphom as, we evaluated 17 PT-LPD to determine whether p16/ INK4a expression could be correlated to morphology, EBV detection, and a Ki-67 labeling index. We demonstrated that tumors with no p16/INK4a expression (n = 8) had a predom inantly monomorphic appearance, and most were EBV negative (respectively, 7 /8 and 5/8), whereas lesions with p16/INK4a expression (n = 9) were mostly polymorphic PT-LPD (6/9) (p = 0.049) and associated with EBV (9/9) (P = 0.0 15). In particular, strong p16/INK4a expression was observed in atypical im munoblasts and Reed-Sternberg-like cells. Furthermore, the proliferation in dex was significantly higher in tumors lacking p16/ INK4a expression than i n other lesions (P = 0.0008). In conclusion, down-regulation of p16/INK4a w as mostly observed in PT-LPD lesions known to follow more aggressive course s: monomorphic tumors and EBV-negative PT-neoplasms. Conversely, overexpres sion of p16/INK4a was associated with EBV-positive PT-LPD. While p16/INK4a might play a role in the proliferative rate of LP-LPD, further investigatio ns are needed to assess the clinical relevance of p16/INK4a expression in p redicting the evolution of tumors and to explain how EBV could favor p16/IN K4a protein accumulation in lesions.