Expression of transforming growth factor alpha in human hepatocellular carcinoma

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Abstract
— Transforming growth factor alpha (TGF-α) is a mitogenic polypeptide which acts on the epidermal growth factor receptor (EGFR). The aim of this study was to examine the expression of TGF-α in human hepatocellular carcinoma (HCC) and surrounding cirrhotic tissue, and to compare it with normal liver. Immunoreactive TGF-α was detected using two antibodies raised against its C terminus, a polyclonal antibody 26T and a monoclonal antibody Ab-2. In normal liver immunoreactive TGF-α was localised strongly to bile duct epithelium and weakly in occasional parenchymal cells but was notably absent from perisinusoidal and Kupffer cells. Eight out of twenty-eight (28%) cases of HCC expressed TGF-α as demonstrated by cytoplasmic staining with both antibodies and in four cases additional membrane immunoreactivity was demonstrated using 26T. However, where cirrhotic tissue surrounding TGF-α positive tumours was available for analysis immunoreactive TGF-α was detected in only 1/7 cases. TGF-α synthesis by malignant hepatocytes was supported by the detection of specific RNA by Northern blotting from two cases with TGF-α immunoreactivity. These results implicate bile duct epithelium as an important source of TGF-α in human liver. Furthermore, in HCC the expression of TGF-α in some cases, together with paucity of TGF-α immunoreactivity in surrounding cirrhotic tissue, suggests that TGF-α may play a role in continued cell proliferation in human hepatocarcinogenesis.