Abstract:
:Cholangiocarcinoma of intrahepatic and extrahepatic bile ducts has a multistep carcinogenesis. Two premalignant lesions have been suggested for invasive cholangiocarcinoma: biliary intraepithelial neoplasia and intraductal papillary neoplasm of the bile duct. How the carcinogenetic process differs between biliary intraepithelial neoplasia and intraductal papillary neoplasm of the bile duct is not clear. In this study, we performed a pathological study to reveal the expression of key molecules related to the cell cycle during 2 carcinogenetic lineages. We immunohistochemically examined the expression of p21, p53, cyclin D1, and Dpc4 in a total of 89 cases: nonneoplastic biliary epithelium, biliary intraepithelial neoplasia, intraductal papillary neoplasm of the bile duct, and invasive cholangiocarcinoma. The expression of p21, p53, and cyclin D1 was up-regulated with histological progression in both biliary intraepithelial neoplasia and intraductal papillary neoplasm of the bile duct, whereas Dpc4 expression was down-regulated in these 2 lineages. In biliary intraepithelial neoplasia, p21 expression was significantly up-regulated early on. In contrast, levels of all molecules changed gradually in intraductal papillary neoplasm of the bile duct. Changes in p53 expression during histological progression differed significantly between biliary intraepithelial neoplasia and intraductal papillary neoplasm of the bile duct. p53 expression was dramatically up-regulated at the invasive stage of biliary intraepithelial neoplasia, whereas it was quite low in noninvasive biliary intraepithelial neoplasia. In contrast, p53 expression was already up-regulated in low-grade intraductal papillary neoplasm and reached a plateau in high-grade intraductal papillary neoplasm and invasive cholangiocarcinoma. This study suggested p21, p53, cyclin D1, and Dpc4 to be involved in the carcinogenesis of both biliary intraepithelial neoplasia and intraductal papillary neoplasm of the bile duct. p53 expression was regulated differently in biliary intraepithelial neoplasia compared with intraductal papillary neoplasm of the bile duct.
journal_name
Hum Patholjournal_title
Human pathologyauthors
Nakanishi Y,Zen Y,Kondo S,Itoh T,Itatsu K,Nakanuma Ydoi
10.1016/j.humpath.2007.11.018subject
Has Abstractpub_date
2008-08-01 00:00:00pages
1153-61issue
8eissn
0046-8177issn
1532-8392pii
S0046-8177(07)00687-9journal_volume
39pub_type
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