Chilosi M, Doglioni C, Menestrina F, Montagna L, Rigo A, Lestani M, Barbareschi M, Scarpa A, Mariuzzi G M, Pizzolo G
Istituto di Anatomia Patologica, Università di Verona, Italy.
Blood. 1994 Dec 15;84(12):4295-300.
The possible involvement of p53 tumor suppressor gene in the pathogenesis of Hodgkin's disease (HD) is suggested by the frequent finding of abnormal accumulation of p53 protein in the nuclei of Reed-Sternberg cells and their variants (H-RS) in a large proportion of cases. This finding, besides being consistent with the presence of p53 gene mutations, might represent a consequence of the inactivating interaction between p53 and p53-binding proteins such as the product of the MDM2 cellular oncogene. We have examined an unselected series of 77 HD cases of different histologic patterns for the expression of p53 and MDM2 proteins, using specific monoclonal antibodies and sensitive immunohistochemical techniques in single- and double-marker combination. In the large majority of cases (66/77), a variable proportion of H-RS cells expressed MDM2 that was strictly confined to the nuclei. Coexpression of both MDM2 and p53 was common in the same cells. The abnormal nuclear expression of p53 and MDM2 did not seem to correlate with the presence of Epstein-Barr virus infection, as shown by the results of LMP-1 antigen expression and EBER in situ hybridization analysis. Our data suggest that the abnormal accumulation of MDM2 and p53 proteins in HD might reflect a derangement of molecular mechanisms that could play a pathogenetic role in this disease.
在大部分病例中，经常发现里德-斯腾伯格细胞及其变异细胞（霍奇金-里德-斯腾伯格细胞）的细胞核中p53蛋白异常积聚，这提示p53肿瘤抑制基因可能参与了霍奇金淋巴瘤（HD）的发病机制。这一发现，除了与p53基因突变的存在相一致外，可能还代表了p53与p53结合蛋白（如MDM2细胞癌基因产物）之间失活相互作用的结果。我们使用特异性单克隆抗体和灵敏的免疫组织化学技术，以单标记和双标记组合的方式，对77例不同组织学类型的未经选择的HD病例进行了p53和MDM2蛋白表达检测。在大多数病例（66/77）中，不同比例的霍奇金-里德-斯腾伯格细胞表达MDM2，且严格局限于细胞核。MDM2和p53在同一细胞中共表达很常见。LMP-1抗原表达和EBER原位杂交分析结果显示，p53和MDM2的异常核表达似乎与爱泼斯坦-巴尔病毒感染的存在无关。我们的数据表明，HD中MDM2和p53蛋白的异常积聚可能反映了分子机制的紊乱，而这可能在该疾病的发病中起致病作用。
