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Expression of cell cycle-related molecules in biliary premalignant lesions: biliary intraepithelial neoplasia and biliary intraductal papillary neoplasm.
Hum Pathol 2008; 39(8):1153-61HP

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.

Authors+Show Affiliations

Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa 920-8640, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

18495210

Citation

Nakanishi, Yoshitsugu, et al. "Expression of Cell Cycle-related Molecules in Biliary Premalignant Lesions: Biliary Intraepithelial Neoplasia and Biliary Intraductal Papillary Neoplasm." Human Pathology, vol. 39, no. 8, 2008, pp. 1153-61.
Nakanishi Y, Zen Y, Kondo S, et al. Expression of cell cycle-related molecules in biliary premalignant lesions: biliary intraepithelial neoplasia and biliary intraductal papillary neoplasm. Hum Pathol. 2008;39(8):1153-61.
Nakanishi, Y., Zen, Y., Kondo, S., Itoh, T., Itatsu, K., & Nakanuma, Y. (2008). Expression of cell cycle-related molecules in biliary premalignant lesions: biliary intraepithelial neoplasia and biliary intraductal papillary neoplasm. Human Pathology, 39(8), pp. 1153-61. doi:10.1016/j.humpath.2007.11.018.
Nakanishi Y, et al. Expression of Cell Cycle-related Molecules in Biliary Premalignant Lesions: Biliary Intraepithelial Neoplasia and Biliary Intraductal Papillary Neoplasm. Hum Pathol. 2008;39(8):1153-61. PubMed PMID: 18495210.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Expression of cell cycle-related molecules in biliary premalignant lesions: biliary intraepithelial neoplasia and biliary intraductal papillary neoplasm. AU - Nakanishi,Yoshitsugu, AU - Zen,Yoh, AU - Kondo,Satoshi, AU - Itoh,Tomoo, AU - Itatsu,Keita, AU - Nakanuma,Yasuni, Y1 - 2008/05/20/ PY - 2007/07/18/received PY - 2007/11/27/revised PY - 2007/11/30/accepted PY - 2008/5/23/pubmed PY - 2008/8/30/medline PY - 2008/5/23/entrez SP - 1153 EP - 61 JF - Human pathology JO - Hum. Pathol. VL - 39 IS - 8 N2 - 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. SN - 1532-8392 UR - https://www.unboundmedicine.com/medline/citation/18495210/Expression_of_cell_cycle_related_molecules_in_biliary_premalignant_lesions:_biliary_intraepithelial_neoplasia_and_biliary_intraductal_papillary_neoplasm_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0046-8177(07)00687-9 DB - PRIME DP - Unbound Medicine ER -