Expression of p16/INK4a in posttransplantation lymphoproliferative disorders

Am J Pathol. 2000 May;156(5):1573-9. doi: 10.1016/S0002-9440(10)65029-8.


It was recently demonstrated that classification of posttransplantation lymphoproliferative disorders (PT-LPDs) into morphological and molecular categories is clinically relevant. It was also reported that PT-LPD not associated with Epstein-Barr virus (EBV) had a more aggressive course than most lesions associated with EBV. Because the cyclin-dependent kinase inhibitor p16/INK4a has been reported to be frequently inactivated in high-grade lymphomas, 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 predominantly 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 = 0.015). In particular, strong p16/INK4a expression was observed in atypical immunoblasts and Reed-Sternberg-like cells. Furthermore, the proliferation index was significantly higher in tumors lacking p16/INK4a expression than in other lesions (P = 0.0008). In conclusion, down-regulation of p16/INK4a was mostly observed in PT-LPD lesions known to follow more aggressive courses: monomorphic tumors and EBV-negative PT-neoplasms. Conversely, overexpression 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 investigations are needed to assess the clinical relevance of p16/INK4a expression in predicting the evolution of tumors and to explain how EBV could favor p16/INK4a protein accumulation in lesions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Blotting, Southern
  • Carrier Proteins / analysis*
  • Carrier Proteins / genetics
  • Clone Cells
  • Cyclin-Dependent Kinase Inhibitor p16
  • DNA / genetics
  • DNA / metabolism
  • DNA Methylation
  • DNA, Viral / genetics
  • Epstein-Barr Virus Infections / virology
  • Female
  • Gene Expression Regulation
  • Heart Transplantation / adverse effects
  • Herpesvirus 4, Human / genetics
  • Humans
  • Immunohistochemistry
  • Ki-67 Antigen / analysis
  • Kidney Transplantation / adverse effects
  • Liver Transplantation / adverse effects
  • Lung Transplantation / adverse effects
  • Lymphoproliferative Disorders / etiology
  • Lymphoproliferative Disorders / metabolism*
  • Lymphoproliferative Disorders / pathology
  • Male
  • Middle Aged
  • Organ Transplantation / adverse effects*


  • Carrier Proteins
  • Cyclin-Dependent Kinase Inhibitor p16
  • DNA, Viral
  • Ki-67 Antigen
  • DNA