The Loss of E-cadherin is Associated with the Epigenetic Alteration of CDH1 in Breast Cancer and it is also Associated with an Abnormal beta-catenin Expression in Lobular Carcinoma.

Gwangil Kim; Ji Young Kim; Hee Jung An; Haeyoun Kang; Tae Heon Kim; Jung Yon Shim; Jin Hyung Heo; Hai Lin Park; Young Kil Choi

doi:10.4132/KoreanJPathol.2009.43.5.400

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Original Article The Loss of E-cadherin is Associated with the Epigenetic Alteration of CDH1 in Breast Cancer and it is also Associated with an Abnormal beta-catenin Expression in Lobular Carcinoma.: Gwangil Kim, Ji Young Kim, Hee Jung An, Haeyoun Kang, Tae Heon Kim, Jung Yon Shim, Jin Hyung Heo, Hai Lin Park, Young Kil Choi; Journal of Pathology and Translational Medicine 2009;43(5):400-407
DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.5.400

¹Department of Pathology, Bundang CHA Medical Center, School of Medicine, CHA University, Seongnam, Korea. blacknw@hanmail.net
²Department of Pathology, Gangnam CHA Medical Center, School of Medicine, CHA University, Seoul, Korea.
³Department of Surgery, Gangnam CHA Medical Center, School of Medicine, CHA University, Seoul, Korea.
⁴Department of Internal Medicine, Gangnam CHA Medical Center, School of Medicine, CHA University, Seoul, Korea.

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Abstract

BACKGROUND
APC and E-cadherin are the key molecules in the Wnt/beta-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
Sixty-four 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, beta-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 beta-catenin (p=0.042). APC methylation was positively correlated with the ER expression (p=0.021). Abnormal cytoplasmic localization of beta-catenin was found in 10 cases and any expression was not detected in six cases. In ILCs, the E-cadherin or beta-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 beta-catenin expression was related to the loss of E-cadherin in ILC.

Keywords: Breast neoplasms;Wnt1 protein;Beta catenin;DNA methylation;E-cadherin

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