肝细胞癌及癌旁肝组织中PTEN表达与MAPK磷酸化的相关性

目的：研究肝细胞癌（HCC）及癌旁肝组织中PTEN表达与丝裂素激活的蛋白激酶（mitogen-activated protein kinase,MAPK)磷酸化的相关性。方法：利用SP免疫组织化学检测75例HCC及其癌旁肝组织中PTEN蛋白和p42/44^MAPK的表达。结果：①HCC中PTEN蛋白的阳性率（62．7％）和阳性强度明显低于癌旁肝组织（89．3％）（P＜0．01），且阳性信号强度与HCC分化程度相关（P＜0．01），即HCC分化愈差，PTEN蛋白表达愈弱。②HCC中p42/44^MAPK的阳性率（85．3％）和表达强度明显高于癌旁肝组织（34．7％）（P＜0．01），但阳性信号强度与癌细胞分化程度无关（P＞0．05）。③相关性分析表明，HCC及癌旁肝组织中PTEN蛋白表达强度和MAPK磷酸化程度呈明显负相关（P＜0．01）。结论：提示在HCC发生中，可能是由于PTEN蛋白表达降低或缺失，不能有效抑制由致癌因子异常激活的Ras/Raf/MAPK信号转导通路，从而使肝细胞异常增殖和发生恶性转化。

Relationship between the expression of PTEN protein and phosphorylation of MAPK in hepatocellular carcinomas and their surrounding liver tissues]

OBJECTIVE: To investigate the relationship between the expression of phosphatase and tensin homolog deleted on chromosome ten(PTEN) protein and phosphorylation of mitogen-activated protein kinase (MAPK) in hepatocellular carcinomas (HCC) and their surrounding liver tissues. METHODS: The expression of PTEN and the phosphorylation of MAPK were detected by the SP immunohistochemical technique in 75 cases of HCC and their pericarcinomatous tissues. RESULTS: The positive rate (62.7%) and the expression intensity of PTEN in HCC were lower and weaker than those in the pericarcinomatous liver tissues (89.3%)(P < 0.01), and the expression level of PTEN was significantly related to the differentiation degree of HCC. The poorer the differentiation of HCC, the weaker the expression of PTEN protein. The positive rate (85.3%) and the expression intensity of p42/44MAPK in HCC were higher and stronger than those in the pericarcinomatous liver tissues (34.7%)(P < 0.01), and the expression intensity of p42/44MAPK was not related to the differentiation degree of HCC. A significant negative relationship was observed between the expression intensity of PTEN protein and the phosphorylation level of MAPK in HCC and their surrounding liver tissues. CONCLUSION: The decrease or deletion of PTEN protein expression may not be able to effectively inhibit the over-activation of Ras/Raf/MAPK signaling pathway, and this will result in abnormal proliferation and malignant transformation of hepatocytes in hepatocellular carcinogenesis.