Hepatocellular carcinoma (HCC) is the most common primary cancer of the liver
(80-90% of primary hepatic carcinomas) approximately one million deaths each year,
predominantly in the underdeveloped and developing countries. HBV and HCV
infection, the cell proliferation and the expression of the apoptosis-related genes (Bcl-2
and p53) have been suggested to be important factors in the genesis of HCC. Thus, this
study was suggested to study the incidence of viral infection in HCC and its
relationship with the expression of p53 and Bcl-2 protein antigens. METHODS: This
study was performed on 45 patients (30 males and 15 females) diagnosed as HCC
cytologically and histopathologically. All patients were screened for the level of serum
alfa-fetoprotein (AFP) using the enzyme-immunoassay (EIA) and tested for hepatitis B
surface antigen (HBsAg) and for hepatitis C virus antibodies (anti-HCV) using the
enzyme-linked immunosorbent assay (ELISA) in addition to routine liver function
tests. p53 and Bcl-2 antigens were studied in serum using ELISA. Further
investigations were performed by special staining and immunohistochemical staining
including eosin and hematoxylin, silver staining (AgNOR), p53 and Bcl-2 antigens.
RESULTS: It was found that the high prevalence of serum p53 antigen concentration
and p53 immunostaining seemed to correlate with HCC grade suggesting that mutant
p53 seems to intervene in the progress of HCC through various grades of increasing
malignancy. The expression of Bcl-2 protein was inversely proportional with the HCC
grade thus, Bcl-2 may be abnormally expressed in some hepatocellular carcinomas
especially in those with low grade. Bcl-2 was remarkably up-regulated in HCC
patients with immunopositive p53, but was down-regulated in patients with
immunonegative p53. This finding is supported by the positive linear correlation we
found between serum Bcl-2 and serum p53 concentrations (P<0.05) in the present study. These results suggest that Bcl-2 and p53 expression are seemed to be
proportionally correlated in HCC cases. The present study also showed that p53 and
Bcl-2 protein overexpression, detected in serum and tissues, in HCC patients positive
for hepatitis B or C or both was greater as compared to that observed in negative
patients. Furthermore, the overexpression of these two proteins in serum and tissues
was more frequently associated with HBV infection than HCV infection.
CONCLUSION: hepatitis B virus and hepatitis C virus may be involved in
hepatocarcinogenesis in patients with HCC. These viral infections may be responsible,
at least in a part, for the mutational change in the p53 gene and may affect the
expression of the Bcl-2 protein in HCC patients.