Alpha-Fetoprotein (AFP)
Historical Overview
The protein that would later be called alpha-fetoprotein (AFP) was first identified in human fetal sera by Bergstrand and Czar in 1956 on paper electrophoregrams (1). Several confirmations of this finding were made, but the potential role of the protein remained entirely unknown. In 1960, the present authors found an antigen in mouse hepatoma cells that was absent from the liver, blood, and other tissues of normal adult mice. However, the relationship of this antigen to a feto-specific serum protein was only established, unexpectedly, during the course of other study on antigenic maturation of mouse liver in ontogenesis.
The "specific hepatoma antigen" was found in tremendous amounts first in embryonal liver extract, then in embryonal serum, and finally in the blood sera of hepatoma-bearing mice. Very soon, it became clear that mouse hepatomas produce and secrete into the blood an embryo-specific serum protein. It was shown in the same work that a short-term wave-like appearance of the protein takes place at liver regeneration. The authors presented these findings at the VIIIth World Cancer Congress in July 1962 in Moscow (2,3). The next year, Tatarinov demonstrated embryo-specific alpha globulin in the serum of patients with hepatocellular carcinoma (HCC) (4). A few years later, it became clear that AFP is a valuable marker in the differential diagnosis of HCC. An important contribution to this problem was made by extensive studies in West Africa (5) and various other African regions (6). Moreover, it was found during clinical studies that AFP is also associated with teratoblastoma of the testis and ovary germ cell tumors (GCT) (7,8).
The next few years brought very broad confirmation and extension of the first clinical observations, with early demonstration of the value of the AFP test in monitoring surgery and chemotherapy, primarily in GCT (8). Very active parallel investigations were carried out on rat and...