The Loss of E-cadherin is Associated with the Epigenetic Alteration of CDH1 in Breast Cancer and it is also Associated with an Abnormal β-catenin Expression in Lobular Carcinoma
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Background : APC and E-cadherin are the key molecules in the Wnt/β-catenin pathway. We attempted to define the epigenetic alteration of APC and CDH1 (the E-cadherin gene) and the expression of Wnt-related molecules in human mammary carcinomas. Methods : Sixtyfour mammary carcinomas, including 52 invasive ductal carcinomas (IDCs) and 12 invasive lobular carcinomas (ILCs), were evaluated using methylation-specific PCR and immunohistochemistry. We performed immunohistochemistry for E-cadherin, β-catenin, APC, Wnt1, cyclin D1, ER, PR and C-erb B2. Results : Hypermethylation of APC and CDH1 was observed in 38 (59%) and 28 (44%) cases, respectively. CDH1 hypermethylation in ILCs was increased compared to that in IDCs (p=0.002) and it was associated with the loss of E-cadherin (p=0.02) and β-catenin (p=0.042). APC methylation was positively correlated with the ER expression (p=0.021). Abnormal cytoplasmic localization of β-catenin was found in 10 cases and any expression was not detected in six cases. In ILCs, the E-cadherin or β-catenin expression was markedly decreased compared to that in IDCs (p<0.001 in both). Conclusions : Methylation of APC or CDH1 was relatively frequent in mammary carcinomas. The loss of E-cadherin in mammary carcinoma was associated with CDH1 methylation, and abnormal β-catenin expression was related to the loss of E-cadherin in ILC.
Abstract
Background : APC and E-cadherin are the key molecules in the Wnt/β-catenin pathway. We attempted to define the epigenetic alteration of APC and CDH1 (the E-cadherin gene) and the expression of Wnt-related molecules in human mammary carcinomas. Methods : Sixtyfour mammary carcinomas, including 52 invasive ductal carcinomas (IDCs) and 12 invasive lobular carcinomas (ILCs), were evaluated using methylation-specific PCR and immunohistochemistry. We performed immunohistochemistry for E-cadherin, β-catenin, APC, Wnt1, cyclin D1, ER, PR and C-erb B2. Results : Hypermethylation of APC and CDH1 was observed in 38 (59%) and 28 (44%) cases, respectively. CDH1 hypermethylation in ILCs was increased compared to that in IDCs (p=0.002) and it was associated with the loss of E-cadherin (p=0.02) and β-catenin (p=0.042). APC methylation was positively correlated with the ER expression (p=0.021). Abnormal cytoplasmic localization of β-catenin was found in 10 cases and any expression was not detected in six cases. In ILCs, the E-cadherin or β-catenin expression was markedly decreased compared to that in IDCs (p<0.001 in both). Conclusions : Methylation of APC or CDH1 was relatively frequent in mammary carcinomas. The loss of E-cadherin in mammary carcinoma was associated with CDH1 methylation, and abnormal β-catenin expression was related to the loss of E-cadherin in ILC.
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