Korean J Pathol.
2006 Feb;40(1):9-16.
Expression of the 14-3-3 sigma Protein and Methylation Status of the 14-3-3 sigma gene in Biliary Neoplasms
- Affiliations
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- 1Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul 138-736, Korea. esyu@amc.seoul.kr
- 2Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul 138-736, Korea.
- 3Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, Seoul 138-736, Korea.
- 4Department of Biological Sciences and Bio/Molecular Informatics Center, Konkuk University, Seoul, Korea.
Abstract
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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.
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