Surface, core, and X genes of hepatitis B virus in hepatocellular carcinoma: an in situ hybridization study

Cancer. 2003 Feb 25;99(1):63-7. doi: 10.1002/cncr.10954.

Abstract

Background: The incidence of hepatocellular carcinoma (HCC) and the seroprevalence of hepatitis B virus (HBV) in this disease state are significantly higher in South India than in North India. Because data on serologic studies do not project the actual association between the two parameters, this study was undertaken.

Methods: The prevalence of HBV genes in HCC patients was studied using nonisotopic in situ hybridization. Fifty patients from South India were diagnosed with HCC after performing ultrasound-guided fine-needle aspiration biopsies of liver lesions. The diagnosis was confirmed by cell block studies. Sections cut from paraffin-embedded cell blocks made out of the aspirates were probed with digoxigenin-labeled surface, core, and X regions of the viral genome.

Results: Nuclear integration of the surface gene was observed in 100% (50 of 50), the core gene was positive in 94% (47 of 50), and the X gene was present in 98% (49 of 50) of the cases. An episomal form of the virus was not found. Serum hepatitis B surface antigen was positive only in 48% (12 of 25) of the patients screened.

Conclusions: We found molecular evidence that HBV is an important contributing factor in the etiology of HCC in South India. In HCC, the S gene of the virus was the most prevalent followed by the X and C genes. Only integrated forms of the viral DNA were observed. Nonisotopic in situ hybridization using multiple regions of the viral genome is a good technique for studying this association. It has an added advantage over polymerase chain reaction, of localization of signals in a tumor cell. Cell blocks made from fine-needle aspirates are ideal for in situ hybridization.

MeSH terms

  • Adult
  • Aged
  • Biopsy, Needle
  • Carcinoma, Hepatocellular / epidemiology
  • Carcinoma, Hepatocellular / etiology
  • Carcinoma, Hepatocellular / virology*
  • DNA, Viral / analysis
  • Female
  • Hepatitis B / complications*
  • Hepatitis B virus / genetics*
  • Hepatitis B virus / pathogenicity
  • Humans
  • In Situ Hybridization
  • Incidence
  • India / epidemiology
  • Liver Neoplasms / epidemiology
  • Liver Neoplasms / etiology
  • Liver Neoplasms / virology*
  • Male
  • Middle Aged
  • Polymerase Chain Reaction
  • Seroepidemiologic Studies

Substances

  • DNA, Viral