Korean J Pathol.  2009 Oct;43(5):400-407. 10.4132/KoreanJPathol.2009.43.5.400.

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

Affiliations
  • 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.

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.

Keyword

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

MeSH Terms

beta Catenin
Breast
Breast Neoplasms
Cadherins
Carcinoma, Ductal
Carcinoma, Lobular
Cyclin D1
Cytoplasm
DNA Methylation
Epigenomics
Immunohistochemistry
Methylation
Polymerase Chain Reaction
Wnt1 Protein
Cadherins
Cyclin D1
Wnt1 Protein
beta Catenin
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