原癌基因mdm2及p53基因与眼眶横纹肌肉瘤生物学特性研究

目的　探讨原癌基因mdm2、p5 3基因在眼眶横纹肌肉瘤 (ORMS)发病机制中的可能作用 ,初步论证mdm2、p5 3作为ORMS生物学特性标记物和预后指标的可行性。方法　应用免疫组化法检测 31例ORMS标本中mdm2、p5 3、Ki 6 7蛋白的表达 ,Ki 6 7蛋白表达作为增殖指标反映肿瘤细胞的增殖状态。应用原位杂交方法检测 31例ORMS标本中mdm2、p5 3基因在mRNA水平的表达。分析mdm2、p5 3蛋白表达与年龄、性别、病理类型、分化程度、增殖程度等临床组织病理学指标之间的关系。结果　 31例ORMS中 ,mdm2、p5 3蛋白水平表达阳性率分别为 77 4 % (2 4 / 31)和 71 0 % (2 2 / 31) ,mdm2与p5 3蛋白共同表达阳性率是 6 1 3%。mdm2、p5 3在蛋白水平表达与其各自的mRNA水平表达之间具有较好一致性。 (1)按肿瘤细胞分化程度分为高、中、低 3个组 :中、低分化组mdm2蛋白阳性率和mdm2与p5 3蛋白共同表达阳性率均较高分化组高 ,差异有显著意义 (P =0 0 0 7、0 0 0 9)。 (2 )按Ki 6 7表达与否分为高、低增殖组 :高增殖组p5 3蛋白表达阳性率较低增殖组高 ,差异有显著意义 (P =0 0 4 4 )。mdm2、p5 3蛋白表达与其他临床病理学指标之间无显著相关性 (P >0 0 5 )。结论　mdm2和p5 3与ORMS的分化和增殖密切相关 ,mdm2与p5 3共同表达提示mdm

Clinical significance of mdm2 and p53 expression in orbital rhabdomyosarcoma

Objective To evaluate the role of oncogene mdm2 and p53 in the development of orbital rhabdomyosarcoma (ORMS) and demonstrate the feasibility of mdm2 and p53 as biological characteristic markers and prognostic indicators.Methods Immunostainings of mdm2, p53 and Ki-67 antigen were performed on archival paraffin-embedded tissues taken from 31 ORMS patients. In situ hybridization was used to demonstrate the expression of mdm2 and p53 on the mRNA level. The correlations between the two genes and the clinical histopathologic parameters including age, gender, cells subtype, differentiation grade and proliferation index were analyzed.Results The positive expressions of mdm2 and p53 were 77.4% (24/31) and 71.0% (22/31) respectively; and the co-expression of mdm2 and p53 was 61.3%. The expressions of mdm2 and p53 on the protein level were in coincidence with that on the mRNA level. (1)The poorly and moderately differentiated group showed significantly higher expression of mdm2 and co-expression of mdm2-p53 than the well-differentiated group (P=0.007; P=0.009, respectively). (2) The samples were divided into actively-proliferating group and inactively-proliferating group in accordance with the expression of Ki-67 protein. The positive expression of p53 was significantly higher in actively-proliferating group than inactively-proliferating group. No statistic correlation of the positive expression of mdm2 and p53 with the other histopathologic parameters was observed.Conclusions mdm2 and p53 were significantly correlated with the differentiation and proliferation of ORMS. The co-expression of mdm2 and p53 expression suggested that mdm2 might play a role in deactivation of p53.The overexpression of mdm2 and p53 leaded to the loss of cell cycle control and may contribute to the tumorigenesis and tumor progression of ORMS. Mdm2 and p53 may be prognostic indicators of the tumor.