Expression of the 14-3-3 sigma Protein and Methylation Status of the 14-3-3 sigma gene in Biliary Neoplasms.
- Author:
Dong Eun SONG
1
;
Se Jin JANG
;
Jung Sun KIM
;
Sang Soo LEE
;
Myung Hwan KIM
;
Seung Gyu LEE
;
Young Joo LEE
;
Hae Joung PARK
;
Yhong Hee SHIM
;
Eunsil YU
Author Information
1. Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul 138-736, Korea. esyu@amc.seoul.kr
- Publication Type:Original Article
- Keywords:
14-3-3 proteins;
Bile ducts;
Biliary tract neoplasms;
Immunohistochemistry;
Methylation
- MeSH:
14-3-3 Proteins;
Bile Ducts;
Biliary Tract Neoplasms;
Carcinogenesis;
Cell Cycle;
Cholangiocarcinoma;
Cytoplasm;
Down-Regulation;
Humans;
Immunohistochemistry;
Liver;
Methylation*
- From:Korean Journal of Pathology
2006;40(1):9-16
- CountryRepublic of Korea
- Language:English
-
Abstract:
BACKGROUND: The 14-3-3 sigma (sigma) protein has a negative regulatory role in the cell cycle progression of the. Down-regulation or overexpression of the 14-3-3 sigma protein has been reported in various human cancers. METHODS: Immunohistochemistry for the 14-3-3 sigma protein was performed in non-neoplastic bile duct cells, intraductal papillary neoplasms of the liver (IPNL), mass-forming intrahepatic cholangiocarcinomas (ICC) and non-papillary extrahepatic cholangiocarcinomas (ECC). We investigated the methylation status of the 14-3-3 sigma gene in 45 cases of these 3 tumor groups. RESULTS: The non-neoplastic bile duct cells demonstrated negative or weakly positive cytoplasmic immunoreactivity for the 14-3-3 sigma protein and no methylation of the 14-3-3 sigma gene. Overexpression as well as negative immunoreactivity associated with hypermethylation of the 14-3-3 sigma protein was observed in 16 (69.6%) of 23 cases of IPNL, in 21 (63.6%) of 33 cases of mass-forming ICC and in 27 (71.1%) of 38 cases of non-papillary ECC. Negative immunoreactivity was increased in the invasive IPNL (4/6, 66.7%), as well as in the poorly differentiated cases of mass-forming ICC (8/12, 66.7%) and the non-papillary ECC (5/8, 62.5%). CONCLUSIONS: The similar rates for the abnormal expression of the 14-3-3 sigma protein among the three groups of biliary neoplasms indicate its general association with biliary carcinogenesis. Furthermore, the loss of the 14-3-3 sigma protein may be involved in the tumor progression and differentiation in the biliary carcinogenesis.