title: Comparative protein expression profiles of hilar and peripheral hepatic cholangiocarcinomas.
abstract: OBJECTIVE
  Hepatic cholangiocarcinomas are tumors with poor prognosis and with increasing incidence worldwide. The aim of the study was to compare morphological features and protein profiles of hilar and peripheral cholangiocarcinomas.
  
  
  METHODS
  Clinicopathological data were collected from 111 cholangiocarcinomas (59 peripheral and 52 hilar). Protein expression, assessed on tissue samples using tissue microarray and protein array technologies, was compared between both types of tumors and with extrahepatic cholangiocarcinoma and hepatocholangiocarcinoma.
  
  
  RESULTS
  Hilar cholangiocarcinomas were smaller in size (mean: 2.7 vs. 8 cm, p<0.001), were more often well differentiated adenocarcinomas (65% vs. 36% well differentiated, p<0.01) and carried out stronger perineural invasion (83% vs. 42%, p<0.001) than peripheral cholangiocarcinomas. Regarding protein expression, hilar cholangiocarcinomas more often expressed MUC5AC (62% vs. 22%, p<0.0001), Akt2 (54% vs. 27%, p<0.001), CK8 (98% vs. 81%, p<0.005) and annexin II (92% vs. 66%, p<0.001). Interestingly, VEGF A expression was more frequently encountered in peripheral cholangiocarcinoma (69% vs. 25%, p<0.0001) and correlated with increased vascular density. Using protein array antibody, we identified filamin A as significantly overexpressed (>2-fold) in peripheral cholangiocarcinomas.
  
  
  CONCLUSIONS
  Our results show that hilar and peripheral cholangiocarcinomas display specific protein profiles, especially regarding VEGF expression. This suggests a potential benefit for anti-angiogenic therapies in peripheral hepatic CCs.
authors.affiliation: Department of Pathology, Beaujon Hospital, 100 boulevard du Général Leclerc, 92118 Clichy, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Guedj
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhan
authors.forename: Martine
authors.initials: M
authors.lastname: Perigny
authors.forename: Pierre-Emmanuel
authors.initials: PE
authors.lastname: Rautou
authors.forename: Françoise
authors.initials: F
authors.lastname: Degos
authors.forename: Jacques
authors.initials: J
authors.lastname: Belghiti
authors.forename: Olivier
authors.initials: O
authors.lastname: Farges
authors.forename: Pierre
authors.initials: P
authors.lastname: Bedossa
authors.forename: Valérie
authors.initials: V
authors.lastname: Paradis
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018281:Cholangiocarcinoma / Q000098:blood supply / Q000737:chemistry* / Q000473:pathology; D003285:Contractile Proteins / Q000032:analysis; D005260:Female; D064448:Filamins; D006801:Humans; D007150:Immunohistochemistry; D053539:Keratin-19 / Q000032:analysis; D008113:Liver Neoplasms / Q000098:blood supply / Q000737:chemistry* / Q000473:pathology; D008297:Male; D008840:Microfilament Proteins / Q000032:analysis; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis*; D012189:Retrospective Studies; D046888:Tissue Array Analysis; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis
chemical_list: D003285:Contractile Proteins; D064448:Filamins; D053539:Keratin-19; D008840:Microfilament Proteins; D009363:Neoplasm Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A