Horie S, Endo K, Kawasaki H, Terada T
Department of Pathology (II), Tottori University, Faculty of Medicine, Yonago, Japan.
Virchows Arch. 2000 Jul;437(1):25-30. doi: 10.1007/s004280000201.
Aberration of the p53 gene is thought to be the most frequent genetic alteration in human cancers. Tp53 protein may be inactivated by the binding of the MDM2 protein. MDM2, the product of the mdm2 gene, is an oncoprotein that binds to Tp53 and inhibits the p53-mediated transactivation. MDM2 overexpression has been reported in several human cancers, but not in intrahepatic cholangiocarcinoma (ICC). Therefore, we have evaluated the immunohistochemical overexpression of MDM2 and the relationship between its expression and histological grade, clinicopathological features, Tp53 overexpression, and Ki-67 labeling index in 47 cases of ICC. MDM2 and Tp53 were found to be overexpressed in 38% and 57% of the tumor, respectively. MDM2 and Tp53 were not expressed in non-tumorous liver tissue. There was no significant difference between the MDM2 overexpression and ICC tumor grade. However, MDM2 overexpression correlated with the presence of metastases (P<0.01) and advanced tumor stage (P<0.05). MDM2 overexpression also correlated with Tp53 overexpression (P<0.03) and Ki-67 labeling index (P<0.03). Our findings suggest that MDM2 overexpression may play a role in the late stage of human ICC.
p53基因畸变被认为是人类癌症中最常见的基因改变。Tp53蛋白可能因与MDM2蛋白结合而失活。MDM2是mdm2基因的产物，是一种癌蛋白，它与Tp53结合并抑制p53介导的反式激活。已有报道称MDM2在几种人类癌症中过表达，但在肝内胆管癌（ICC）中未见过表达。因此，我们评估了47例ICC中MDM2的免疫组化过表达及其表达与组织学分级、临床病理特征、Tp53过表达和Ki-67标记指数之间的关系。结果发现，MDM2和Tp53在38%和57%的肿瘤中过表达。非肿瘤性肝组织中未检测到MDM2和Tp53的表达。MDM2过表达与ICC肿瘤分级之间无显著差异。然而，MDM2过表达与转移的存在（P<0.01）和肿瘤晚期（P<0.05）相关。MDM2过表达还与Tp53过表达（P<0.03）和Ki-67标记指数（P<0.03）相关。我们的研究结果表明，MDM2过表达可能在人类ICC的晚期发挥作用。
