Background: Transforming growth factor-alpha (TGF-alpha) is a potent stimulator of cell proliferation in the liver and in liver tumors; however, its significance and association with hepatocyte proliferation remains unclear.
Methods: Expression of TGF-alpha and proliferation markers, such as proliferating cell nuclear antigen (PCNA) and cyclin A, were studied and correlated with each other in samples of tumor and surrounding liver tissue taken from nine patients with hepatoblastoma. An avidin-biotin-peroxidase immunohistochemical method was used for detection of TGF-alpha, PCNA, and cyclin A, and in situ hybridization was used to detect TGF-alpha mRNA.
Results: Two types of tumor cells of epithelial origin were distinguished based on the expression of TGF-alpha protein and RNA. The more differentiated "fetal" phenotype had a high expression of TGF-alpha and correlated with a low expression of proliferation markers. The less differentiated "embryonal" phenotype had low TGF-alpha expression and high proliferation activity.
Conclusions: The expression of TGF-alpha is associated with a certain morphologic phenotype of tumor cells in hepatoblastoma; higher expression can be detected in more differentiated tumor cells. The negative correlation between the expression of TGF-alpha and proliferation markers suggests that the less differentiated embryonal cells do not depend on growth stimulation provided by TGF-alpha.