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.
10.4132/KoreanJPathol.2009.43.5.400
- Author:
Gwangil KIM
1
;
Ji Young KIM
;
Hee Jung AN
;
Haeyoun KANG
;
Tae Heon KIM
;
Jung Yon SHIM
;
Jin Hyung HEO
;
Hai Lin PARK
;
Young Kil CHOI
Author Information
1. Department of Pathology, Bundang CHA Medical Center, School of Medicine, CHA University, Seongnam, Korea. blacknw@hanmail.net
- Publication Type:Original Article
- Keywords:
Breast neoplasms;
Wnt1 protein;
Beta catenin;
DNA methylation;
E-cadherin
- MeSH:
beta Catenin;
Breast;
Breast Neoplasms;
Cadherins;
Carcinoma, Ductal;
Carcinoma, Lobular;
Cyclin D1;
Cytoplasm;
DNA Methylation;
Epigenomics;
Immunohistochemistry;
Methylation;
Polymerase Chain Reaction;
Wnt1 Protein
- From:Korean Journal of Pathology
2009;43(5):400-407
- CountryRepublic of Korea
- Language:English
-
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.