Hepatitis C virus infection associated with human hepatocellular carcinoma: lack of correlation with p53 abnormalities in Caucasian patients.
BACKGROUND
Several lines of evidence indicate that there is a close association between hepatitis C virus (HCV) infection and hepatocellular carcinoma (HCC). However, the role of the virus itself in the development of the disease is not yet well understood.


METHODS
In liver samples from 15 anti-HCV positive Caucasian patients with HCC, the authors searched for the presence and genomic characteristics of the infecting virus, and also analyzed the p53 gene by single strand conformation polymorphism and sequencing of abnormal bands.


RESULTS
In all cases but one, HCV RNA was detected in nonneoplastic liver tissue, whereas in neoplastic tissue, viral sequences were detected in 6 of 6 samples containing moderately differentiated HCC (Edmondson grades I-II) and in 2 of 9 containing poorly differentiated HCC (Edmondson grade III) (P=0.007). Seventy-three percent of the cases were infected by genotype 1 and 20% by genotype 2, whereas the liver cells of 1 patient with a previous history of hepatitis B infection were HCV RNA negative. p53 mutations, observed in 2 patients, consisted of a G-to-A transition at codon 176 of exon 5 in 1 patient and a G-to-T transversion at codon 287 of exon 8 in the other.


CONCLUSIONS
The results of this study indicate that HCV may contribute to liver tumor development during the early stages of carcinogenesis, whereas p53 gene mutations were detected only in 2 of 15 patients in this cohort.
Dipartimento di Medicina Clinica e Sperimentale, Università di Padova, Italy.
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P
Pontisso
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C
Belluco
R
R
Bertorelle
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L
De Moliner
L
L
Chieco-Bianchi
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D
Nitti
M
M
Lise
A
A
Alberti
D000225:Adenine; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000150:complications* / Q000235:genetics / Q000821:virology; D003062:Codon / Q000235:genetics; D015331:Cohort Studies; D004279:DNA, Viral / Q000032:analysis / Q000235:genetics; D005091:Exons / Q000235:genetics; D005260:Female; D016158:Genes, p53 / Q000235:genetics*; D016679:Genome, Viral; D005838:Genotype; D006147:Guanine; D016174:Hepacivirus / Q000235:genetics*; D006509:Hepatitis B / Q000235:genetics; D006526:Hepatitis C / Q000150:complications* / Q000235:genetics; D006801:Humans; D008113:Liver Neoplasms / Q000150:complications* / Q000235:genetics / Q000821:virology; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D018807:Polymorphism, Single-Stranded Conformational; D012367:RNA, Viral / Q000032:analysis / Q000235:genetics; D017422:Sequence Analysis, DNA; D013941:Thymine; D044465:White People / Q000235:genetics*
D003062:Codon; D004279:DNA, Viral; D012367:RNA, Viral; D006147:Guanine; D000225:Adenine; D013941:Thymine