SV40 Tag DNA sequences, present in a small proportion of human hepatocellular carcinomas, are associated with reduced survival.
OBJECTIVE
To study the association between simian virus 40 (SV40) and human hepatocarcinogenesis.


METHODS
Polymerase chain reaction (PCR) to detect SV40 large T antigen (Tag) DNA was performed on: 50 human hepatocellular carcinoma (HCCs) diagnosed between 1978 and 1989 (cohort A); 20 cases of alcoholic liver cirrhosis from the same period; and 20 HCCs diagnosed after 1997 (cohort B). PCR to detect SV40 regulatory sequence and SV40 Tag immunohistochemistry were performed on selected cases from cohorts A and B. Amplified products were directly sequenced. Immunohistochemistry for p53 and pRb and clinicopathological analyses were performed on selected cases from cohorts A and B. Complete survival data were collected for cohort A.


RESULTS
SV40 Tag DNA was found in five cohort A HCCs but not in alcoholic liver cirrhosis cases or cohort B HCCs. Neither SV40 regulatory sequence nor SV40 Tag protein were demonstrated in Tag DNA positive HCCs. No clinicopathological differences existed between Tag DNA positive and negative HCCs, but the presence of Tag DNA was associated with reduced disease specific survival. Relatively fewer Tag DNA positive than negative HCCs expressed p53, but loss of pRb expression was similar in the two groups. Patients with Tag DNA positive HCCs were unlikely to have received SV40 contaminated poliovirus vaccine.


CONCLUSIONS
SV40 Tag DNA is present in a small proportion of historical HCCs and may contribute to their pathogenesis and influence their outcome. The source of the virus is uncertain and more recent HCCs show no evidence of SV40.
Wong
N A C S
NA
Department of Pathology, University of Edinburgh Medical School, Edinburgh EH8 9AG, UK. newton.wong@cancer.org.uk
Rae
F
F
Herriot
M M
MM
Mayer
N J
NJ
Brewster
D H
DH
Harrison
D J
DJ
D000368:Aged; D000369:Aged, 80 and over; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics*; D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000401:mortality / Q000821:virology; D015331:Cohort Studies; D004279:DNA, Viral / Q000235:genetics*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008113:Liver Neoplasms / Q000235:genetics* / Q000401:mortality / Q000821:virology; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction / Q000379:methods; D027601:Polyomavirus Infections / Q000150:complications / Q000235:genetics*; D013539:Simian virus 40 / Q000235:genetics / Q000276:immunology*; D016019:Survival Analysis; D014412:Tumor Virus Infections / Q000150:complications / Q000235:genetics*
D000952:Antigens, Polyomavirus Transforming; D004279:DNA, Viral