We investigated whether regulation of interferon-alpha gene expression
could be involved in liver tumor biology an the role, if any, of hepa
titis B virus in the regulation of tumor cytokine gene expression. Gen
e expression was investigated at the transcriptional level using 'in s
itu' hybridization of cytokine message with an interferon-alpha cDNA p
robe and at the translational level with immunohistochemistry using an
immunoperoxidase technique. Compared to histologically normal liver,
a greater percentage of tumor and non-tumor-involved liver tissue sect
ions (67-80% vs. 17%) contained cells positive for interferon-alpha me
ssenger RNA, many of which were also seen to contain an increased numb
er of transcripts (> 100 grains/cell). Hepatitis B infection did not a
ppear to play a role in gene activation, at the hepatocellular level,
in liver disease. Except for sinusoidal cells, cells containing cytoki
ne transcripts also produced mature immunoreactive protein. Absence of
interferon-alpha protein within mononuclear and sinusoidal cells in s
eronegative hepatocellular carcinoma tissue with/without underlying li
ver disease suggested deficient cytokine gene expression, at the post
transcriptional level, within these cells in this group. Bile duct epi
thelia in tumor tissue were found to contain immunoreactive protein fo
r interferon-alpha. In summary our results suggest that interferon-alp
ha gene activation in hepatocellular carcinoma occurs as a result of t
he liver cell damage and does not play a dominant role in tumor biolog
y.