巨噬细胞移动抑制因子和细胞周期蛋白D1的表达与肝细胞癌生长和转移的关系

目的研究巨噬细胞移动抑制因子（MIF）、细胞周期蛋白D1（Cyclin D1）、细胞周期蛋白依赖激酶4（CDK4）、磷酸化视网膜母细胞瘤易感基因产物蛋白（phospho—Rb）在HeC组织中的表达及其与癌细胞生长和转移的关系。方法应用组织芯片技术和免疫组织化学方法检测93份HCC组织中MIF、Cyclin D1、CDK4和phospho—Rb的表达，分析它们的表达与HCC临床病理特征的关系。结果93份HCC组织中MIF、Cyclin D1、CDK4和phospho—Rb的表达率分别为71％、41％、82％和14％，MIF和Cyclin D1阳性表达率与正常肝脏组织表达率之间的差异有统计学意义（P〈0．01），CDK4和phospho—Rb阳性表达率与正常肝脏组织表达率之间的差异无统计学意义（P〉0．05）。在≥3．5cm的肿瘤中MIF表达率为79％，明显高于在〈3．5cm肿瘤中的表达率48％（P〈0．01）；有转移的肝癌组织中Cyclin D1阳性率为62％，明显高于无转移组织中的阳性率35％，差异有统计学意义（P〈0．05）。MIF表达强弱与Cyclin D1的表达呈正相关关系（P〈0，01）。CDK4和phospho—Rb的表达与肿瘤大小及是否转移的关系无统计学意义。结论MIF和Cyclin D1在HCC发展进程中可能促进肿瘤的生长和转移。

Correlations of expressions of macrophage migration inhibitor factor and cyclin D1 with tumor size and metastasis of hepatocellular carcinoma

OBJECTIVE: To explore the possible relationship between the expressions of macrophage migration inhibitor factor (MIF), cyclin D1, cyclin-dependent kinase 4 (CDK4), phosphorylated-retinoblastoma susceptibility gene product Rb protein (phospho-Rb) and the development of hepatocellular carcinoma (HCC). METHODS: 93 HCC tissues and 5 normal liver tissues were used to investigate the expressions of MIF, cyclin D1, CDK4 and phospho-Rb by tissue microarray and immunohistochemistry methods. RESULTS: The expression rates of MIF, cyclin D1, CDK4 and phospho-Rb in the HCC tissues were 71%, 41%, 82% and 14% respectively, and in the normal liver tissues, they were 0%, 0%, 80% and 20% respectively. The expression rates of MIF and cyclin D1 were significantly different between the tumor and the normal liver tissues and the expression rates of CDK4 and phospho-Rb were not significantly different between the tumor and the normal liver tissues. The rate difference (69% versus 48%) of MIF expression between the larger tumors (> 3.5 cm) and the smaller tumors (< 3.5 cm) was of statistical significance (P < 0.01). The expression rate (62%) of cyclin D1 in the tumors with metastasis was significantly higher than the expression rate (35%) in the tumors without metastasis (P < 0.05). MIF expression was positively correlated with cyclin D1 expression in the tumor tissues (P < 0.01). CDK4 and phospho-Rb expressions were not significantly associated with the tumor sizes and metastasis status. CONCLUSION: Our results indicate that MIF and cyclin D1 might be related to the growth and metastasis of HCC.