title: Annexin A1: A new immunohistological marker of cholangiocarcinoma.
abstract: OBJECTIVE
  To evaluate a new immunohistological marker, annexin A1 (ANXA1), in cholangiocarcinoma (CCA) and hepatocellular carcinoma (HCC).
  
  
  METHODS
  Expression of ANXA1 protein was investigated in liver tissues from patients with CCA and HCC by immunohistochemistry. Its expression on differences stages of tumor development was investigated in hamster CCA tissues induced by Opisthorchis viverrini and N-nitrosodimethylamine. Moreover, mRNA expression of ANXA1 was assessed in CCA cell lines by quantitative real-time polymerase chain reaction and silencing of ANXA1 gene expression using small interfering RNA.
  
  
  RESULTS
  In human CCA tissue arrays, immunohistochemical analysis revealed that the positive expression of ANXA1 was 94.1% (64/68 cases) consisting of a high expression (66.2%, 45/68 cases) and a low expression (33.8%, 23/68 cases). However, expression of ANXA1 protein was negative in all histologic patterns for HCC (46/46 cases) and healthy individuals (6/6 cases). In hamster with opisthorchiasis-associated CCA, the expression of ANXA1 was observed in the cytoplasm of inflammatory cells, bile duct epithelia and tumor cells. Grading scores of ANXA1 expression were significantly increased with tumor progression. In addition, mRNA expression of ANXA1 significantly increased in all of the various CCA cell lines tested compared to an immortalized human cholangiocyte cell line (MMNK1). Suppressing the ANXA1 gene significantly reduced the matrix metalloproteinase (MMP) 2 and MMP9, and transforming growth factor-β genes, but increased nuclear factor-κB gene expression.
  
  
  CONCLUSIONS
  ANXA1 is highly expressed in CCA, but low in HCC, suggesting it may serve as a new immunohistochemical marker of CCA. ANXA1 may play a role in opisthorchiasis-associated cholangiocarcinogenesis.
authors.affiliation: Department of Parasitology, Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.
authors.forename: Nuttanan
authors.initials: N
authors.lastname: Hongsrichan
authors.forename: Rucksak
authors.initials: R
authors.lastname: Rucksaken
authors.forename: Yaovalux
authors.initials: Y
authors.lastname: Chamgramol
authors.forename: Porntip
authors.initials: P
authors.lastname: Pinlaor
authors.forename: Anchalee
authors.initials: A
authors.lastname: Techasen
authors.forename: Puangrat
authors.initials: P
authors.lastname: Yongvanit
authors.forename: Narong
authors.initials: N
authors.lastname: Khuntikeo
authors.forename: Chawalit
authors.initials: C
authors.lastname: Pairojkul
authors.forename: Somchai
authors.initials: S
authors.lastname: Pinlaor
mesh_terms: D000818:Animals; D017305:Annexin A1 / Q000235:genetics / Q000378:metabolism*; D001650:Bile Duct Neoplasms / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000469:parasitology / Q000473:pathology; D001653:Bile Ducts, Intrahepatic / Q000378:metabolism* / Q000469:parasitology / Q000473:pathology; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D001706:Biopsy; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D018281:Cholangiocarcinoma / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000469:parasitology / Q000473:pathology; D006224:Cricetinae; D004128:Dimethylnitrosamine; D004195:Disease Models, Animal; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology; D008297:Male; D008647:Mesocricetus; D008875:Middle Aged; D009891:Opisthorchis / Q000472:pathogenicity; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D046888:Tissue Array Analysis; D014162:Transfection
chemical_list: D017305:Annexin A1; D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D004128:Dimethylnitrosamine
keywords: Annexin A1; Biomarker; Cholangiocarcinoma; Hepatocellular carcinoma; Opisthorchis viverrini