Clonal origin of multifocal hepatocellular carcinoma.
BACKGROUND
Hepatocellular carcinoma is the most common primary tumor of the liver. Patients frequently have multiple histologically similar, but anatomically separate tumors. The clonal origin of multiple hepatocellular carcinomas is uncertain.


METHODS
The authors analyzed 31 tumors from 12 different patients (11 women, 1 man), who had multiple hepatocellular carcinomas involving 1 or both lobes. Genomic DNA was extracted from formalin-fixed, paraffin-embedded tissue using laser capture microdissection. DNA was analyzed for loss of heterozygosity (LOH), X chromosome inactivation status, and TP53 gene mutations.


RESULTS
Ten (83%) of the 12 patients showed LOH in at least 1 of the analyzed microsatellite markers. Concordant LOH patterns between separate hepatocellular carcinomas in individual patients were seen in 8 (80%) of 10 cases, whereas discordant patterns were seen in 2 (20%) of 10 cases. Five (50%) of 10 informative female patients showed identical nonrandom X chromosome inactivation patterns in multiple tumors; 1 case showed discordant nonrandom X chromosome inactivation pattern. TP53 mutations were identified in 8 (67%) of 12 patients. Tumors in 7 (88%) of these 8 patients showed different point mutations. Three patients (Cases 4, 5, and 10) had tumors with additional TP53 point mutations, indicating additional genetic abnormalities in these tumors.


CONCLUSIONS
The data suggested that the significant proportion of patients with multifocal hepatocellular carcinomas have tumors of common clonal origin.
Hodges
Kurt B
KB
Departments of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana.
Cummings
Oscar W
OW
Saxena
Romil
R
Wang
Mingsheng
M
Zhang
Shaobo
S
Lopez-Beltran
Antonio
A
Montironi
Rodolfo
R
Nour
Hammam
H
Cheng
Liang
L
D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D005260:Female; D016158:Genes, p53; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics*; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D009154:Mutation; D049951:X Chromosome Inactivation