Transforming growth factor-alpha in human hepatocellular carcinoma and coexpression with hepatitis B surface antigen in adjacent liver

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Abstract
Background. Hepatitis B virus (HBV) infection is closely associated with the development of hepatocellular carcinoma (HCC) in many patients, but the mechanisms by which HBV contributes to HCC are not known. Transforming growth factor-alpha (TGF-α), a regulator of growth and regeneration in rat liver that can be found in high levels in some human cancers, theoretically could play such an intermediate role in the development of HCC. Methods. The expression of TGF-α and its relation to the HBV antigens were evaluated in human HCC and adjacent nontumorous livers from 33 patients from the United States and China using immunoperoxidase staining of paraffin-embedded sections. Results. TGF-α was detected in HCC from 27 of 33 (82%) patients; the frequencies were similar in patients from the United States and China. TGF-α was detected in HCC more frequently in patients whose adjacent nontumorous livers had detectable hepatitis B surface antigen (HBs Ag) and/or hepatitis B core antigen (HBc Ag) than in those whose adjacent livers lacked HBs Ag and HBc Ag. Detection of TGF-α was not affected by tumor size, histologic type, or grade. TGF-α was detected in adjacent nontumorous livers from 31 of 33 patients (94%). Coexpression at a high intensity of TGF-α and HBs Ag in the same hepatocytes could be demonstrated by specific staining of consecutively cut sections for 17 of 33 patients (52%). Conclusions. TGF-α is expressed at a high level in 82% of human HCC. Localization of HBs Ag within the same hepatocytes as TGF-a suggests a possible interaction between HBV and TGF-α during hepatocarcinogenesis in humans. Stimulation of TGF-α expression could be part of a chain of events by which HBV contributes to the development of HCC in some patients.