胃癌中Wnt信号通路的激活及E-cadherin/catenins的异常表达

ACTIVATION OF Wnt SIGNALING PATHWAY AND THE ABNORMAL EXPRESSION OF THE E-cadherin/catenins IN GASTRIC CARCINOMA

目的探讨胃癌中Wnt信号通路与E-cadherin/catenins复合体的关联性及其与胃癌浸润转移的关系,为指导临床治疗与判断预后提供有价值的分子指标。方法应用免疫组织化学SP法检测Wnt2、β-catenin、α-catenin、E-cadherin在胃癌中的表达及流式细胞术测定β-catenin在胃不同组织中的总含量。结果胃癌中β-catenin出现膜表达缺失,浆表达增强,总表达量下降;Wnt2呈强表达,而α-catenin、E-cadherin出现膜表达缺失。β-catenin的异位表达与淋巴结转移及肿瘤浸润深度有关,Wnt2的表达仅与肿瘤的浸润深度有关,α-catenin的异常表达仅与病理分级有关,E-cadherin的异常表达与肿瘤的浸润深度、淋巴结转移、病理分级、临床分期有关。结论胃癌中Wnt信号通路处于激活状态,E-cadherin/catenins复合体表达也明显异常,并通过影响β-catenin的细胞内分布,与Wnt传导通路产生交互协同作用,共同影响胃癌的发生、侵袭、转移进程。

Objective To investigate the relationship of Wnt signaling pathway and E-cadherin/catenins as well as their roles in the invasion and metastasis of gastric carcinoma in order to provide valuable molecule marker to clinical diagnoses and prognoses. Methods The expression of Wnt2,β-catenin, E-cadherin and a-catenin were detected by immunohistochemistry while the expression of β-catenin in different groups was detected by flow cytometry. Results In gastric carcinoma, the expression of β-catenin in cell membrane was absent and conversely that in cytoplasm was increased,and the general expression was decreased. The expression of Wnt2 was obviously stronger in gastric carcinoma. The expression of E-cadherin and a-catenin in cell membrane were absent. The abnormal expression of β-catenin was stronger in the groups with deep invasion and lymphatic metastasis. The expression of Wnt2 was only correlated with invasion depth and the abnormal expression of a-catenin was only correlated with pathologic classification. While the abnormal expression of E-cadherin was correlated with invasion depth, lymphatic metastasis,and clinical stage. Conclusion Wnt signaling pathway in gastric carcinoma group was in a state of activation. The expression of E-cadherin/catenins in carcinoma group was obviously abnormal. E-cadherin/catenins might interact with Wnt signaling pathway through changing the intracellular distribution of β-catenin to affect the invasion and metastasis of gastric carcinoma.