title: Role of CD56-expressing immature biliary epithelial cells in biliary atresia.
abstract: OBJECTIVE
  To analyze the clinical and pathological parameters and expression of the neural cell adhesion molecule (CD56) in patients with biliary atresia (BA).
  
  
  METHODS
  Established clinical laboratory markers of hepatic function, including enzyme activity, protein synthesis, and bilirubin metabolism, were evaluated in patients with BA and compared with those in patients with choledochal cysts and neonatal hepatitis. Pathological changes in tissue morphology and fibrosis were examined by histological and tissue collagen staining. Immunohistochemical staining for the biliary epithelial cell markers CD56 and CK19 together with the Notch signaling related molecules Notch1 and Notch2 was performed in the context of alterations in the structure of intrahepatic biliary ducts.
  
  
  RESULTS
  Differences in some clinical laboratory parameters among the three diseases examined were observed, but they did not correlate with the pathological classification of fibrosis in BA. Immunohistochemical staining showed the presence of CD56-positive immature bile ducts in most patients (74.5%) with BA but not in patients with choledochal cysts or neonatal hepatitis. The number of CD56-expressing cells correlated with disease severity, with more positive cells present in the later stages of liver damage (81.8% vs 18.2%). Furthermore, bile plugs were mainly found in CD56-positive immature biliary ducts. Notch signaling was a key regulatory pathway in biliary duct formation and played a role in tissue fibrosis. Notch1 was co-expressed in CD56-positive cells, whereas Notch2 was found exclusively in blood vessels in the portal area of patients with BA.
  
  
  CONCLUSIONS
  The maturation of biliary epithelial cells and the expression of Notch may play a role in the pathogenesis of BA.
authors.affiliation: Rui-Zhong Zhang, Jia-Kang Yu, Jiao Peng, Yan Chen, Hui-Min Xia, Department of Pediatric Surgery, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong Province, China.
authors.forename: Rui-Zhong
authors.initials: RZ
authors.lastname: Zhang
authors.affiliation: Rui-Zhong Zhang, Jia-Kang Yu, Jiao Peng, Yan Chen, Hui-Min Xia, Department of Pediatric Surgery, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong Province, China.
authors.forename: Jia-Kang
authors.initials: JK
authors.lastname: Yu
authors.affiliation: Rui-Zhong Zhang, Jia-Kang Yu, Jiao Peng, Yan Chen, Hui-Min Xia, Department of Pediatric Surgery, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong Province, China.
authors.forename: Jiao
authors.initials: J
authors.lastname: Peng
authors.affiliation: Rui-Zhong Zhang, Jia-Kang Yu, Jiao Peng, Yan Chen, Hui-Min Xia, Department of Pediatric Surgery, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong Province, China.
authors.forename: Feng-Hua
authors.initials: FH
authors.lastname: Wang
authors.affiliation: Rui-Zhong Zhang, Jia-Kang Yu, Jiao Peng, Yan Chen, Hui-Min Xia, Department of Pediatric Surgery, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong Province, China.
authors.forename: Hai-Ying
authors.initials: HY
authors.lastname: Liu
authors.affiliation: Rui-Zhong Zhang, Jia-Kang Yu, Jiao Peng, Yan Chen, Hui-Min Xia, Department of Pediatric Surgery, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong Province, China.
authors.forename: Vincent C H
authors.initials: VC
authors.lastname: Lui
authors.affiliation: Rui-Zhong Zhang, Jia-Kang Yu, Jiao Peng, Yan Chen, Hui-Min Xia, Department of Pediatric Surgery, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong Province, China.
authors.forename: John M
authors.initials: JM
authors.lastname: Nicholls
authors.affiliation: Rui-Zhong Zhang, Jia-Kang Yu, Jiao Peng, Yan Chen, Hui-Min Xia, Department of Pediatric Surgery, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong Province, China.
authors.forename: Paul K H
authors.initials: PK
authors.lastname: Tam
authors.affiliation: Rui-Zhong Zhang, Jia-Kang Yu, Jiao Peng, Yan Chen, Hui-Min Xia, Department of Pediatric Surgery, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong Province, China.
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Lamb
authors.affiliation: Rui-Zhong Zhang, Jia-Kang Yu, Jiao Peng, Yan Chen, Hui-Min Xia, Department of Pediatric Surgery, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong Province, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Rui-Zhong Zhang, Jia-Kang Yu, Jiao Peng, Yan Chen, Hui-Min Xia, Department of Pediatric Surgery, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong Province, China.
authors.forename: Hui-Min
authors.initials: HM
authors.lastname: Xia
mesh_terms: D001652:Bile Ducts / Q000737:chemistry* / Q000473:pathology; D001656:Biliary Atresia / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D001663:Bilirubin / Q000097:blood; D019002:CD56 Antigen / Q000032:analysis*; D002648:Child; D002675:Child, Preschool; D015529:Choledochal Cyst / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D004847:Epithelial Cells / Q000737:chemistry* / Q000473:pathology; D006505:Hepatitis / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007231:Infant, Newborn; D053539:Keratin-19 / Q000032:analysis; D008103:Liver Cirrhosis / Q000378:metabolism / Q000473:pathology; D008297:Male; D051881:Receptor, Notch1 / Q000032:analysis; D051883:Receptor, Notch2 / Q000032:analysis; D012720:Severity of Illness Index; D005723:gamma-Glutamyltransferase / Q000097:blood
chemical_list: D019002:CD56 Antigen; D053539:Keratin-19; C522918:NCAM1 protein, human; C497761:NOTCH1 protein, human; C497764:NOTCH2 protein, human; D051881:Receptor, Notch1; D051883:Receptor, Notch2; D005723:gamma-Glutamyltransferase; C554782:gamma-glutamyltransferase, human; D001663:Bilirubin
keywords: Biliary atresia; Biliary epithelial cells; CD56; Cytokeratin 7; Epithelial cell adhesion molecule; Liver fibrosis