Comparative protein expression profiles of hilar and peripheral hepatic cholangiocarcinomas.
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.
Guedj
Nathalie
N
Department of Pathology, Beaujon Hospital, 100 boulevard du Général Leclerc, 92118 Clichy, France.
Zhan
Qian
Q
Perigny
Martine
M
Rautou
Pierre-Emmanuel
PE
Degos
Françoise
F
Belghiti
Jacques
J
Farges
Olivier
O
Bedossa
Pierre
P
Paradis
Valérie
V
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
D003285:Contractile Proteins; D064448:Filamins; D053539:Keratin-19; D008840:Microfilament Proteins; D009363:Neoplasm Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A