Hiroki Mori1, Kazunori Masahata2, Satoshi Umeda2, Yuji Morine3, Hiroki Ishibashi3, Noriaki Usui2, Mitsuo Shimada3. 1. Department of Surgery, Institute of Health Biosciences, The University of Tokushima, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan. mori.hiroki@tokushima-u.ac.jp. 2. Department of Pediatric Surgery, Osaka Women's and Children's Hospital, Murodoucho 840, Izumi, Osaka, 594-1101, Japan. 3. Department of Surgery, Institute of Health Biosciences, The University of Tokushima, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan.
Abstract
PURPOSES: Congenital biliary dilatation (CBD), defined as pancreaticobiliary maljunction (PBM) with biliary dilatation, is a high risk factor for biliary tract cancer (BTC). KRAS and p53 mutations reportedly affect this process, but the mechanisms are unclear, as is the likelihood of BTC later in life in children with CBD. We investigated potential carcinogenetic pathways in children with CBD compared with adults. METHODS: The subjects of this study were nine children with CBD and 13 adults with PBM (10 dilated, 3 non-dilated) without BTC who underwent extrahepatic bile duct resections, as well as four control patients who underwent pancreaticoduodenectomy for non-biliary cancer. We evaluated expressions of Ki-67, KRAS, p53, histone deacetylase (HDAC) and activation-induced cytidine deaminase (AID) in the biliary tract epithelium immunohistochemically. RESULTS: The Ki-67 labeling index (LI) and expressions of KRAS, p53, HDAC, and AID in the gallbladder epithelium were significantly higher or tended to be higher in both the children with CBD and the adults with PBM than in the controls. CONCLUSIONS: BTC may develop later in children with CBD and in adults with PBM, via HDAC and AID expression and through epigenetic and genetic regulation.
PURPOSES: Congenital biliary dilatation (CBD), defined as pancreaticobiliary maljunction (PBM) with biliary dilatation, is a high risk factor for biliary tract cancer (BTC). KRAS and p53 mutations reportedly affect this process, but the mechanisms are unclear, as is the likelihood of BTC later in life in children with CBD. We investigated potential carcinogenetic pathways in children with CBD compared with adults. METHODS: The subjects of this study were nine children with CBD and 13 adults with PBM (10 dilated, 3 non-dilated) without BTC who underwent extrahepatic bile duct resections, as well as four control patients who underwent pancreaticoduodenectomy for non-biliary cancer. We evaluated expressions of Ki-67, KRAS, p53, histone deacetylase (HDAC) and activation-induced cytidine deaminase (AID) in the biliary tract epithelium immunohistochemically. RESULTS: The Ki-67 labeling index (LI) and expressions of KRAS, p53, HDAC, and AID in the gallbladder epithelium were significantly higher or tended to be higher in both the children with CBD and the adults with PBM than in the controls. CONCLUSIONS: BTC may develop later in children with CBD and in adults with PBM, via HDAC and AID expression and through epigenetic and genetic regulation.
Authors: Seiki Tashiro; T Imaizumi; H Ohkawa; A Okada; T Katoh; Y Kawaharada; H Shimada; H Takamatsu; H Miyake; T Todani Journal: J Hepatobiliary Pancreat Surg Date: 2003
Authors: S Tanno; T Obara; T Fujii; Y Mizukami; R Shudo; N Nishino; H Ura; A J Klein-Szanto; Y Kohgo Journal: Cancer Date: 1998-07-15 Impact factor: 6.860