乳腺癌组织中E-cadherin、β-catenin及cyclin D1表达的相关性研究

Correlation among Expression of E cadherin, β-catenin, and cyclin D1 in Breast Cancers

背景与目的上皮性钙粘素(E-cadherin)通过连接素(catenins)与细胞骨架相连介导细胞同质粘附反应,β-catenin除与E-cadherin结合介导细胞粘附反应外,还作为Wnt信号转导通路的重要成分与肿瘤发生密切相关。本研究通过检测乳腺癌组织中E-cadherin、β-catenin及cyclinD1的表达,探讨E-cadherin、β-catenin在乳腺癌发生、发展中的意义。方法采用免疫组织化学SP法检测60例乳腺癌组织中E-cadherin、β-catenin、cyclinD1的表达。结果乳腺癌组织中有29例(48.3%)E-cadherin、18例(30.0%)β-catenin正常表达,28例(46.7%)cyclinD1过度表达。E-cadherin正常表达病例中,31.0%(9/29)的病例呈现cyclinD1过度表达,而E-cadherin异常表达病例中,61.3%(19/31)的病例呈现cyclinD1过度表达,E-cadherin异常表达与cyclinD1的过度表达有显著的正相关性(rs=0.303,P<0.05)。有42例癌组织表现出β-catenin的异常表达,其中57.1%(24/42)的病例出现cyclinD1的过度表达,而β-catenin正常膜表达病例中,22.2%(4/18)的病例呈现cyclinD1的过度表达。β-catenin的异常表达与cyclinD1的过度表达有显著的正相关性(rs=0.321,P<0.05)。结论E-cadherin和β-catenin的异常表达可能通过促使或激活cyclinD1的过度表达导致乳腺癌的发生和发展。

BACKGROUND & OBJECTIVE: E cadherin links to the cytoskeleton via catenins and mediates cell cell homophilic adhesion. β catenin not only regulates cell cell adhesion as a protein interacting with cadherin, but also functions as an important component of the Wnt signaling pathway which has been found to be closely associated with tumor formation. This study was performed to examine the expression of E cadherin, β catenin, and cyclin D1 in breast cancer in order to evaluate their possible roles in the formation and progression of breast cancer. METHODS: The alterations of E cadherin, β catenin, and cyclin D1 in 60 cases of breast cancer were determined using highly sensitive SP immunohistochemical method. RESULTS: Normal immunoreactivity of E cadherin and β catenin were observed in 29(48.3%) and 18(30.0%) cases, respectively. Twenty eight cases (46.7%) showed cyclin D1 overexpression. Thirty percent (9/29) of the cases with normal staining of E cadherin showed overexpression of cyclin D1, while 61.3%(19/31) of the cases showed overexpression of cyclin D1 with abnormal staining of E cadherin. Abnormal expression of E cadherin and overexpression of cyclin D1 showed a significantly positive correlation (rs=0.303,P< 0.05). Forty two cases showed abnormal staining of β catenin. Cyclin D1 overexpression was observed in 57.1%(24/42) of these cases with abnormal staining of β catenin, but only observed in 22.2%(4/18) of these cases with normal membranous staining of β catenin. There was a significantly positive correlation between the abnormal expression of β catenin and overexpression of cyclin D1 (rs=0.321,P< 0.05). CONCLUSION: Down regulation of E cadherin and β catenin accumulation in the cytoplasm/nuclear may promote malignant transformation and progression by triggering cyclin D1 overexpression in breast cancer.