Immunohistochemical detection of c-myc and c-erbA products in diethylnitrosamine-induced preneoplastic and neoplastic liver lesions in rats.

An immunohistochemical study of c-myc and c-erbA products (p-myc and p-erbA) in preneoplastic and neoplastic rat liver lesions showed that the longer the time of hepatocarcinogenic treatment, the higher the proportion of lesions, whatever their type, showing p-erbA positive cells (p-erbA+). The proportion of p-myc positive foci (the majority of which are also p-erbA+), which was low at the focus stage, increased at the nodule and tumor stages. The incidence of p-myc positivity (alone or combined with erbA positivity) in the nodules decreased from the nodule to the tumor stage. For tumors, three types of altered phenotypes were found, namely: p-myc+, p-erbA+ or p-myc+/p-erbA+. Nevertheless, there were regions in these tumors that were negative. At a given stage, all types of lesions exhibited about the same incidence of immunopositivity for the two oncogene products (expressed either alone or together), the presence of which did not correlate with proliferative activity. Since the fraction of lesions that undergo full malignant progression is much smaller than the proportion of lesions that express c-myc and/or c-erbA proteins, our data exclude the possibility that increased incidence of p-myc/ and/or p-erbA+ cells might be sufficient for inducing full malignancy. A significant proportion of foci and nodules, and of regions of these lesions and of tumors, were unlabeled, whatever the stage at which they are found. This indicates that, if implicated, the positive phenotype(s) would not be required for the maintenance of those liver alterations.