Increased steady‐state levels of alpha‐fetoprotein mRNA in hepatocellular carcinoma: an analysis by in situ hybridization

Abstract: The molecular basis for the augmented production of alpha‐fetoprotein is unknown. We have used in situ hybridization of alpha‐fetoprotein cDNA to malignant hepatocytes to establish if increased serum alpha‐fetoprotein concentrations are related to detectable steady‐state levels of alpha‐fetoprotein mRNA in hepatocytes. Tumor tissue from four patients with histologically confirmed hepatocellular carcinoma were examined, and the results compared to fetal liver. Northern blot hybridization for alpha‐fetoprotein mRNA in tumor tissue was also analyzed. As expected a high number of grains was observed in fetal liver tissue, indicative of high levels of alpha‐fetoprotein mRNA physiologically present during pre‐natal development. Sections from all patients with high serum concentrations of alpha fetoprotein showed appreciable hybrid formation, which correlated semi‐quantitatively with the serum concentrations. However, hybrids were not detected in a patient with a normal serum alpha‐fetoprotein. The high alpha‐fetoprotein mRNA levels in fetal and neoplastic liver suggest that gene transcription is the mechanism of alpha‐fetoprotein production in malignancy, although the control of this mechanism remains speculative.