MAP4K4在肝细胞癌中的表达及意义

doi:10.3971/j.issn.1000-8578.2011.07.006

摘要: 目的探讨MAP4K4蛋白在肝细胞癌中的表达及临床病理学意义。方法用400例肝细胞癌蜡块标本构建肝细胞癌组织芯片，采用免疫组织化学技术检测MAP4K4蛋白在含400例配对肝细胞癌及癌旁组织的表达，并分析不同临床病理参数中MAP4K4蛋白表达水平的差异。结果在正常肝、肝炎和肝硬化组织中MAP4K4呈一致阴性或弱阳性表达，周围结缔组织、血管和胆管无MAP4K4阳性着色，Kuffer细胞和淋巴细胞生发中心可见阳性染色；异型增生结节的肝细胞中MAP4K4的表达明显强于正常肝、肝炎和肝硬化组织，肝细胞癌组织中MAP4K4表达显著增强，其中过度表达194例(48.5%)，灶性阳性或阴性206例(51.5 %)；HBsAg阳性患者MAP4K4阳性率51.5%（157/305）显著高于阴性患者的38.8% (37/95)(P=0.033)，肿瘤直径≤2 cm的MAP4K4阳性率为31.6%（18/57）显著低于肿瘤直径> 2 cm的51.3%（176/343） (P=0.006)，MAP4K4在不同组织学分级中的阳性率差异有统计学意义(P<0.001)，肝内转移病例的MAP4K4阳性率为55.5%（152/274）显著高于未转移者的33.3%（42/126）(P=0.002)，MAP4K4表达在患者年龄、血清甲胎蛋白浓度、肝硬化、包膜浸润方面差异无统计学意义。结论MAP4K4在肝细胞癌组织中高表达，并且其表达水平与HBV感染状态、肿瘤大小、组织学分级及转移情况可能有一定关系。

Abstract: ObjectiveTo investigate the expression and clinicopathological significance of MAP4K4 (mitogen-activated protein kinase kinase kinase kinase 4, MAP4K4) in hepatocellular carcinoma. Methods We detected the expression of MAP4K4 protein in 400 paired samples of HCC and adjacent tissues through tissue microassay which constructed by 400 paraffin embedded blocks of hepatocellular carcinoma and analyzed the expression level of MAP4K4 protein in different clinicopathological parameters. Results The expression of MAP4K4 was uniformly negative or weakly positive in normal, hepatitis and cirrhosis tissue. There was no positive staining of MAP4K4 in surrounding connective tissue, blood vessel and biliary ducts. Positive staining could be observed in germinal center of Kupffer cells and lympholeukocyte. Compared to the corresponding adjacent tissues, the expression of MAP4K4 was obviously overexpressed in dysplasia nodule cells than that in normal, hepatitis and cirrhosis cells.The expression of MAP4K4 in hepatocellular carcinoma which increased significantly was heterogeneity with the number of overexpressed sample 194(48.5%) and the focus positive or negative 206(51.5%). The positive rate of MAP4K4 in HBsAg carriers was 51.5%（157/305）, significantly higher than those in control group at 38.8% (37/95)(P= 0.033). The positive rate of MAP4K4 in tumor diameter≤2 cm was 31.6%（18/57）, notably lower than tumor diameter > 2 cm, which was 51.3%（176/343） (P= 0.006). The expression of MAP4K4 was significantly different among different histological grading(P<0.001). The positive rate of MAP4K4 in metastasis was 55.5%（152/274）, which was higher than non-metastasis at 33.3%（42/126）(P=0.002). No significant difference was found in the expression of MAP4K4 with different age, serum AFP concentration, degree of liver cirrhosis and capsular infiltration. ConclusionMAP4K4 is generally highly expressed in hepatocellular carcinoma, which may has a certain relationship with HBV infection state, tumor size, histological grade and metastasis status.

MAP4K4在肝细胞癌中的表达及意义

Expression and Significance of MAP4K4 in Hepatocellular Carcinoma