Martin A, Baran-Marzak F, El Mansouri S, Legendre C, Leblond V, Charlotte F, Davi F, Canioni D, Raphaël M
Service d'Anatomie et Cytologie Pathologiques, Unité Propre de l'Enseignement Superieur, Equipe d' Acceuil 1625, Centre Hospitalo Universitaire Avicenne, Bobigny, France.
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.
最近有研究表明，将移植后淋巴细胞增生性疾病（PT-LPD）分为形态学和分子学类别具有临床相关性。还有报道称，与爱泼斯坦-巴尔病毒（EBV）无关的PT-LPD病程比大多数与EBV相关的病变更具侵袭性。由于细胞周期蛋白依赖性激酶抑制剂p16/INK4a在高级别淋巴瘤中常被报道为失活状态，我们评估了17例PT-LPD，以确定p16/INK4a表达是否与形态学、EBV检测及Ki-67标记指数相关。我们发现，无p16/INK4a表达的肿瘤（n = 8）主要表现为单形性外观，且大多数为EBV阴性（分别为7/8和5/8），而有p16/INK4a表达的病变（n = 9）大多为多形性PT-LPD（6/9）（P = 0.049）且与EBV相关（9/9）（P = 0.015）。特别地，在非典型免疫母细胞和里德-施特恩伯格样细胞中观察到p16/INK4a强表达。此外，缺乏p16/INK4a表达的肿瘤增殖指数显著高于其他病变（P = 0.0008）。总之，p16/INK4a下调主要见于已知病程更具侵袭性的PT-LPD病变：单形性肿瘤和EBV阴性的PT肿瘤。相反，p16/INK4a过表达与EBV阳性的PT-LPD相关。虽然p16/INK4a可能在LP-LPD的增殖率中起作用，但需要进一步研究以评估p16/INK4a表达在预测肿瘤演变中的临床相关性，并解释EBV如何促进病变中p16/INK4a蛋白积累。
