Preciado M V, Cristobal E, Menarguez J, Martinez Montero J C, Diez B, De Matteo E, Grinstein S
Laboratory of Virology, Ricardo Gutierrez Children's Hospital, Buenos Aires, Argentina.
Pathol Res Pract. 1998;194(1):25-31. doi: 10.1016/s0344-0338(98)80008-3.
A new category of oncogenes regulating apoptosis, p53 and bcl-2, and the Epstein Barr virus (EBV) latent membrane protein-1 (LMP-1) have been related to Hodgkin's disease (HD) pathogenesis. We attempt to determine p53, mdm2, p21waf-1, bcl-2 and LMP-1 immunohistochemical expression in tissue sections from formalin-fixed, paraffin-embedded lymph node biopsies of pediatric HD. P53 was detected in the nucleus of Reed Sternberg cells and their variants (H-RS) in 68% of the HD cases. However, there was no statistically significant association with either clinical stages or with histological subtypes. P21waf-1, an indirect marker of p53 functional status, showed nuclear labelling of H-RS in all the studied cases. MDM2 co-expressed with p53 in 62% of the cases, suggesting that both proteins regulate one another, in HD by a self regulatory loop. Bcl-2 cytoplasmatic expression in H-RS was demonstrated in 65% of the cases. There was co-expression of bcl-2 and p53 in 51%, but it failed to correlate with a poor prognosis. LMP-1 labelling was shown in 51% of the cases, disclosing a statistically significant association with the under 6-year group (p = 0.005, Fisher's exact test). Since LMP-1 induces the expression of bcl-2 in vitro, the relation of both proteins was analysed and found to co-express in 15/37 cases, with a statistically significant association only in the under 6-year group (p = 0.001, Fisher's exact test). Abnormal accumulation of these oncoproteins in tumour cells could play a role in the pathogenesis of a subset of pediatric HD.
一类新的调控细胞凋亡的癌基因、p53和bcl-2，以及爱泼斯坦-巴尔病毒（EBV）潜伏膜蛋白1（LMP-1）已与霍奇金淋巴瘤（HD）的发病机制相关。我们试图确定p53、mdm2、p21waf-1、bcl-2和LMP-1在福尔马林固定、石蜡包埋的小儿HD淋巴结活检组织切片中的免疫组化表达。在68%的HD病例中，在里德·斯腾伯格细胞及其变异体（H-RS）的细胞核中检测到p53。然而，与临床分期或组织学亚型均无统计学上的显著关联。p21waf-1是p53功能状态的间接标志物，在所有研究病例中均显示H-RS的细胞核标记。在62%的病例中，MDM2与p53共表达，提示在HD中这两种蛋白通过一个自我调节环相互调节。65%的病例中显示H-RS有bcl-2的细胞质表达。51%的病例中bcl-2和p53共表达，但与预后不良无关。51%的病例显示有LMP-1标记，与6岁以下组有统计学上的显著关联（p = 0.005，费舍尔精确检验）。由于LMP-1在体外诱导bcl-2的表达，分析了这两种蛋白的关系，发现15/37例中共表达，仅在6岁以下组有统计学上的显著关联（p = 0.001，费舍尔精确检验）。这些癌蛋白在肿瘤细胞中的异常积累可能在小儿HD的一个亚组发病机制中起作用。
