title: S100P immunostaining identifies a subset of peripheral-type intrahepatic cholangiocarcinomas with morphological and molecular features similar to those of perihilar and extrahepatic cholangiocarcinomas.
abstract: OBJECTIVE
  S100P is a calcium-binding protein that is frequently expressed in pancreatic adenocarcinoma and perihilar cholangiocarcinoma. The aim of this study was to investigate the pathological significance of the expression of S100P in peripheral intrahepatic cholangiocarcinoma (ICC).
  
  
  RESULTS
  Immunohistochemical staining was used to investigate S100P expression in 112 cases of peripheral ICC. The results were compared with those for perihilar and extrahepatic cholangiocarcinomas. Patients with S100P-positive peripheral ICC were more likely to have elevated serum levels of carcinoembryonic antigen (CEA) and CA19-9 than those with S100P-negative peripheral ICCs. All cases of peripheral ICC associated with intrahepatic lithiasis and all cases with intraductal/periductal growth patterns were positive for S100P. S100P-positive peripheral ICCs were highly associated with 'bile duct' morphology rather than cholangiolar differentiation. Nearly all cases of perihilar and extrahepatic cholangiocarcinoma were positive for S100P. Similarly to perihilar and extrahepatic cholangiocarcinomas, S100P-positive peripheral ICCs showed more frequent expression of CEA and MUC2, and were more likely to be N-cadherin-negative, than S100P-negative cases. Notably, K-RAS mutations were only detected in S100P-positive peripheral ICCs, with a frequency similar to that in perihilar and extrahepatic cholangiocarcinomas. Patients with S100P-positive peripheral ICC were more likely to have poor prognoses than those with S100P-negative tumours.
  
  
  CONCLUSIONS
  S100P immunostaining identifies a subset of peripheral ICC that probably originates from larger bile ducts. This subset of peripheral ICCs shares common morphological and molecular features with perihilar and extrahepatic cholangiocarcinomas.
authors.affiliation: Department of Pathology, National Taiwan University Hospital, Taiwan.
authors.forename: Jia-Huei
authors.initials: JH
authors.lastname: Tsai
authors.forename: Wen-Chih
authors.initials: WC
authors.lastname: Huang
authors.forename: Kuan-Ting
authors.initials: KT
authors.lastname: Kuo
authors.forename: Ray-Hwang
authors.initials: RH
authors.lastname: Yuan
authors.forename: Yu-Ling
authors.initials: YL
authors.lastname: Chen
authors.forename: Yung-Ming
authors.initials: YM
authors.lastname: Jeng
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000378:metabolism; D001650:Bile Duct Neoplasms / Q000145:classification / Q000175:diagnosis / Q000378:metabolism*; D017734:Bile Ducts, Extrahepatic; D001653:Bile Ducts, Intrahepatic; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D002272:Carcinoembryonic Antigen / Q000378:metabolism; D018281:Cholangiocarcinoma / Q000145:classification / Q000175:diagnosis / Q000378:metabolism*; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D011379:Prognosis; D012189:Retrospective Studies
chemical_list: D015295:Antigens, Tumor-Associated, Carbohydrate; D014408:Biomarkers, Tumor; D002135:Calcium-Binding Proteins; D002272:Carcinoembryonic Antigen; D009363:Neoplasm Proteins; C103003:S100P protein, human; C578959:carbohydrate antigen 199, human