Bile duct expression of pancreatic and duodenal homeobox 1 in perihilar cholangiocarcinogenesis

Histopathology. 2012 Aug;61(2):266-76. doi: 10.1111/j.1365-2559.2012.04218.x. Epub 2012 May 17.

Abstract

Aims: Pancreatic and duodenal homeobox 1 (Pdx1) is a transcription factor that is crucial in embryogenic development and differentiation of pancreas, and its overexpression is reportedly involved in the progression of many malignancies, including pancreatic carcinoma. In this study, the role of Pdx1 was examined in cholangiocarcinogenesis.

Methods and results: Forty-three cases of human cholangiocarcinoma (CC) and 66 cases of hepatolithiasis or primary sclerosing cholangitis (PSC) with biliary intraepithelial neoplasia (BilIN) lesions and also eight fetal and 20 adult normal livers were examined immunohistochemically. Pdx1 was constantly expressed in the nuclei of fetal bile ducts, but was virtually absent in the large bile ducts of adults. By contrast, Hairy and enhancer of split 1 (Hes1), which represses pancreatic exocrine and endocrine differentiation, was expressed frequently in the adult bile ducts. Pdx1 was expressed in 67% of invasive CCs. In large bile ducts, expression of Pdx1 increased while that of Hes1 decreased during the progression of BilIN lesions to CC. Expression of Pdx1 correlated with proliferative activities in CCs. In an in vitro study, all three CC cell lines expressed Pdx1 mRNA and protein.

Conclusion: Up-regulation of Pdx1 is a feature of cholangiocarcinogenesis associated with chronic cholangitis. Furthermore, expression of Pdx1 in CC is related to increased proliferative activity in CCs.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Base Sequence
  • Bile Duct Neoplasms / genetics
  • Bile Duct Neoplasms / metabolism*
  • Bile Duct Neoplasms / pathology
  • Bile Ducts / embryology
  • Bile Ducts / metabolism
  • Bile Ducts / pathology
  • Bile Ducts, Intrahepatic*
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Carcinoma in Situ / genetics
  • Carcinoma in Situ / metabolism
  • Carcinoma in Situ / pathology
  • Carcinoma, Pancreatic Ductal / genetics
  • Carcinoma, Pancreatic Ductal / metabolism
  • Carcinoma, Pancreatic Ductal / pathology
  • Cell Line, Tumor
  • Cell Proliferation
  • Cholangiocarcinoma / genetics
  • Cholangiocarcinoma / metabolism*
  • Cholangiocarcinoma / pathology
  • Cholangitis, Sclerosing / genetics
  • Cholangitis, Sclerosing / metabolism
  • Cholangitis, Sclerosing / pathology
  • Cholelithiasis / genetics
  • Cholelithiasis / metabolism
  • Cholelithiasis / pathology
  • Female
  • Fetus / metabolism
  • Gene Knockdown Techniques
  • Homeodomain Proteins / antagonists & inhibitors
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism*
  • Humans
  • Immunohistochemistry
  • Liver / embryology
  • Liver / metabolism
  • Liver / pathology
  • Male
  • Middle Aged
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Neoplasm / genetics
  • RNA, Neoplasm / metabolism
  • Trans-Activators / antagonists & inhibitors
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Up-Regulation

Substances

  • Biomarkers, Tumor
  • Homeodomain Proteins
  • RNA, Messenger
  • RNA, Neoplasm
  • Trans-Activators
  • pancreatic and duodenal homeobox 1 protein