Tzardi M, Kouvidou C, Panayiotides I, Stefanaki K, Rontogianni D, Zois E, Koutsoubi K, Eliopoulos G, Delides G, Kanavaros P
Department of Pathology, University Hospital of Heraklion, Heraklion.
Clin Mol Pathol. 1996 Oct;49(5):M278-82. doi: 10.1136/mp.49.5.m278.
Aims-To investigate the pattern of expression of p53 protein and two wild type p53 induced proteins (mdm2 and p21/waf1) as an indirect way of assessing p53 gene status in non-Hodgkin's lymphoma.Methods-Formalin fixed, paraffin wax embedded tissue from 87 cases of nodal non-Hodgkin's lymphoma, comprising 52 high grade and 35 low grade tumours, was stained by immunohistochemistry for p53, mdm2 and p21/waf1 proteins.Results-p53, mdm2 and waf1/p21 proteins were expressed in 36/52, 21/52 and 31/52 high grade and 3/35, 21/35 and 3/35 low grade non-Hodgkin's lymphomas, respectively. Parallel p53/mdm2 protein expression was found in 23 cases (21 high grade and two low grade). These 23 cases were also positive for p21/waf1 protein expression. Discordant p53 positive/mdm2 negative protein expression was found in 16 cases (15 high grade and one low grade). Eleven (10 high grade and one low grade) of these 16 cases were p21/waf1 positive and the remaining five high grade non-Hodgkin's lymphomas were p21/waf1 negative. Mdm2 and p21/waf1 proteins were not expressed in the absence of p53 protein expression.Conclusions-p53, mdm2 and waf1/p21 protein expression is more frequently associated with aggressive histotypes of non-Hodgkin's lymphoma. Parallel expression of p53, mdm2 and p21 proteins may represent non-Hodgkin's lymphomas with a wild type p53 gene as mdm2 and p21 proteins can be induced by the wild type gene. In these cases p53 protein expression may result from stabilisation via complex formation with the mdm2 protein. This could be important in the pathogenesis of these cases as mdm2 may deregulate the p53 dependent growth suppressive pathway. Discordant p53 positive/mdm2 negative/p21 negative protein expression may represent non-Hodgkin's lymphoma with p53 gene mutations unable to activate expression of mdm2 and p21 proteins. Non-Hodgkin's lymphoma with p53 positive/mdm2 negative/p21 positive protein expression may have either wild type p53 with deregulated mdm2 gene expression or mutated p53 gene with p53 independent p21 expression.
目的——研究p53蛋白及两种野生型p53诱导蛋白（mdm2和p21/waf1）的表达模式，以此作为评估非霍奇金淋巴瘤中p53基因状态的间接方法。方法——对87例淋巴结非霍奇金淋巴瘤（包括52例高级别肿瘤和35例低级别肿瘤）经福尔马林固定、石蜡包埋的组织进行免疫组织化学染色，检测p53、mdm2和p21/waf1蛋白。结果——p53、mdm2和waf1/p21蛋白分别在36/52、21/52和31/52例高级别以及3/35、21/35和3/35例低级别非霍奇金淋巴瘤中表达。23例（21例高级别和2例低级别）出现p53/mdm2蛋白平行表达。这23例p21/waf1蛋白表达也呈阳性。16例（15例高级别和1例低级别）出现p53阳性/mdm2阴性蛋白表达不一致情况。这16例中的11例（10例高级别和1例低级别）p21/waf1呈阳性，其余5例高级别非霍奇金淋巴瘤p21/waf1呈阴性。在无p53蛋白表达时，mdm2和p21/waf1蛋白不表达。结论——p53、mdm2和waf1/p21蛋白表达更常与侵袭性组织学类型的非霍奇金淋巴瘤相关。p53、mdm2和p21蛋白的平行表达可能代表具有野生型p53基因的非霍奇金淋巴瘤，因为mdm2和p21蛋白可由野生型基因诱导产生。在这些病例中，p53蛋白表达可能是通过与mdm2蛋白形成复合物而稳定化导致的。这在这些病例的发病机制中可能很重要，因为mdm2可能会使p53依赖性生长抑制途径失调。p53阳性/mdm2阴性/p21阴性蛋白表达不一致可能代表p53基因突变的非霍奇金淋巴瘤，该突变无法激活mdm2和p21蛋白的表达。p53阳性/mdm2阴性/p21阳性蛋白表达的非霍奇金淋巴瘤可能具有mdm2基因表达失调的野生型p53，或者具有p53独立表达的突变型p53基因。
