Clinical and molecular analysis of combined hepatocellular-cholangiocarcinomas.
OBJECTIVE
Combined hepatocellular-cholangiocarcinoma (HCC-CC) show dual hepatocellular and biliary epithelial differentiation. To better understand the relations between cholangiocarcinoma (CC), HCC-CC and hepatocellular carcinoma (HCC), we screened for genetic alterations.


METHODS
A series of nine CC, 15 HCC-CC and three separated HCC and CC lesions ('collision tumors') were screened for loss of heterozygosity (LOH) using 400 microsatellite markers and for p53 and beta-catenin mutations. A comparison with a previously characterized series of 137 HCC was performed.


RESULTS
In six cases of CC and HCC-CC, we identified TP53 gene mutations. A CTNNB1/beta-catenin was identified in two patients presenting collision tumors, but no mutations were found in CC or in HCC-CC. A high level of chromosome instability in both CC and HCC-CC was found. Recurrent specific LOH were identified at 3p and 14q in more than 50% of the CC and the HCC-CC cases, whereas these chromosomal regions were deleted in less than 10% of the HCC cases (P<10(-5)). Minimal common regions of deletion (MCRD) were defined at 3p24-p14 and 14q24-q32, respectively.


CONCLUSIONS
These results suggest that combined HCC-CC are genetically closer to CC than HCC and common carcinogenesis pathways may be altered in HCC-CC and CC.
Department of Pathology, Hôpital Beaujon, AP-HP, 92110 Clichy, France.
Dominique
D
Cazals-Hatem
Sandra
S
Rebouissou
Paulette
P
Bioulac-Sage
Olivier
O
Bluteau
Hélène
H
Blanché
Dominique
D
Franco
Geneviève
G
Monges
Jacques
J
Belghiti
Antonio
A
Sa Cunha
Pierre
P
Laurent-Puig
Claude
C
Degott
Jessica
J
Zucman-Rossi
D000368:Aged; D000483:Alleles; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D018281:Cholangiocarcinoma / Q000235:genetics* / Q000473:pathology; D043171:Chromosomal Instability; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D003598:Cytoskeletal Proteins / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D016158:Genes, p53; D015894:Genome, Human; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D009154:Mutation; D015534:Trans-Activators / Q000235:genetics; D051176:beta Catenin
C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D015534:Trans-Activators; D051176:beta Catenin