Expression of p16/INK4a in posttransplantation lymphoproliferative disorders.
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.
Martin
A
A
Service d'Anatomie et Cytologie Pathologiques, Unité Propre de l'Enseignement Superieur, Equipe d' Acceuil 1625, Centre Hospitalo Universitaire Avicenne, Bobigny, France. antoine.martin@avc.ap-hop-paris.fr
Baran-Marzak
F
F
El Mansouri
S
S
Legendre
C
C
Leblond
V
V
Charlotte
F
F
Davi
F
F
Canioni
D
D
Raphaël
M
M
D000328:Adult; D000368:Aged; D015139:Blotting, Southern; D002352:Carrier Proteins / Q000032:analysis* / Q000235:genetics; D002999:Clone Cells; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004247:DNA / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation; D004279:DNA, Viral / Q000235:genetics; D020031:Epstein-Barr Virus Infections / Q000821:virology; D005260:Female; D005786:Gene Expression Regulation; D016027:Heart Transplantation / Q000009:adverse effects; D004854:Herpesvirus 4, Human / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis; D016030:Kidney Transplantation / Q000009:adverse effects; D016031:Liver Transplantation / Q000009:adverse effects; D016040:Lung Transplantation / Q000009:adverse effects; D008232:Lymphoproliferative Disorders / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016377:Organ Transplantation / Q000009:adverse effects*
D002352:Carrier Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004279:DNA, Viral; D019394:Ki-67 Antigen; D004247:DNA