Expression of the 14-3-3 sigma Protein and Methylation Status of the 14-3-3 sigma gene in Biliary Neoplasms.

Song,  Dong Eun; Jang,  Se Jin; Kim,  Jung Sun; Lee,  Sang Soo; Kim,  Myung Hwan; Lee,  Seung Gyu; Lee,  Young Joo; Park,  Hae Joung; Shim,  Yhong Hee; Yu,  Eunsil

Original Article

The Korean Journal of Pathology 2006;40(1): 9-16.

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