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The Korean Journal of Pathology 2006;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.
Dong Eun Song, 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
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
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.
Key Words: 14-3-3 proteins; Bile ducts; Biliary tract neoplasms; Immunohistochemistry; Methylation