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

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±è±¤ÀÏ, ±èÁö¿µ, ¾ÈÈñÁ¤, °­ÇýÀ±, ±èÅÂÇå, Shim Jung-Yon, ÇãÁøÇü, ¹ÚÇظ°, ÃÖ¿µ±æ,
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±è±¤ÀÏ ( Kim Gwang-Il ) 
Æ÷õÁß¹®ÀÇ°ú´ëÇб³ º´¸®Çб³½Ç

±èÁö¿µ ( Kim Ji-Young ) 
Æ÷õÁß¹®ÀÇ°ú´ëÇб³ °­³²Â÷º´¿ø º´¸®°ú
¾ÈÈñÁ¤ ( Ahn Hee-Jung ) 
Æ÷õÁß¹®ÀÇ°ú´ëÇб³ ºÐ´çÂ÷º´¿ø º´¸®Çб³½Ç
°­ÇýÀ± ( Kang Hae-Youn ) 
Æ÷õÁß¹®ÀÇ°ú´ëÇб³ ºÐ´çÂ÷º´¿ø º´¸®°ú
±èÅÂÇå ( Kim Tae-Heon ) 
Æ÷õÁß¹®ÀÇ°ú´ëÇб³ º´¸®Çб³½Ç
 ( Shim Jung-Yon ) 
Æ÷õÁß¹®ÀÇ°ú´ëÇб³ °­³²Â÷º´¿ø º´¸®°ú
ÇãÁøÇü ( Heo Jin-Hyung ) 
Æ÷õÁß¹®ÀÇ°ú´ëÇб³ ºÐ´çÂ÷º´¿ø º´¸®°ú
¹ÚÇظ° ( Park Hai-Lin ) 
Æ÷õÁß¹®ÀÇ°ú´ëÇб³ ¿Ü°úÇб³½Ç
ÃÖ¿µ±æ ( Choi Young-Kil ) 
Æ÷õÁß¹®ÀÇ°ú´ëÇб³ Â÷º´¿ø ³»°ú

Abstract


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

Å°¿öµå

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

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