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(American Journal of Pathology. 2000;156:1573-1579.)
© 2000 American Society for Investigative Pathology

Regular Articles

Expression of p16/INK4a in Posttransplantation Lymphoproliferative Disorders

Antoine Martin^*, Fanny Baran-Marzak, Said El Mansouri, Christophe Legendre, Véronique Leblond^§, Frédéric Charlotte^¶, Frédéric Davi^||, Danielle Canioni^** and Martine Raphaël

From the Service d’Anatomie et Cytologie Pathologiques,^*
Unité Propre de l’Enseignement Superieur, Equipe d’ Acceuil 1625,
and the Service d’Hématologie Biologique,
Centre Hospitalo Universitaire Avicenne, Unité de Formation de Recherche en Santé Médicine Biologie Humaine, Université Paris; the Service d’Hématologie,^§
the Service d’Anatomie et Cytologie Pathologiques,^¶
and the Service d’Hématologie Biologique,^||
Centre Hospitalo Universitaire Pitié-Salpêtrière; and the Service d’Anatomie et Cytologie Pathologiques,^**
Hôpital Necker, Paris, France

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.

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