alpha-Fetoprotein in the routine clinical laboratory: evaluation of a simple radioimmunoassay and review of current concepts in its clinical application.

We have assessed the clinical utility of a radioimmunoassay for alpha-fetoprotein (AFP). The method, which relies on ammonium sulfate precipitation for the separation of "bound" and "free" radiolabeled antigen, can be completed in one working day. The assay is specific for AFP, has a sensitivity of < 10 ng/ml, and has intra- and inter-assay precision of 5--8% and 9--11%, respectively. We have conducted a three-year study of 472 pregnancies in which physicians wished to detect neural tube defects, and of 400 non-pregnant patients to assess the value of serum AFP as a marker for certain benign and malignant diseases. Six of 6 fetal open neural-tube defects (NTD's) and 3 of 3 intrauterine fetal deaths were correctly identified by their association with marked AFP elevations in both maternal serum and amniotic fluid. Thirty non-pregnant patients were found to have AFP elevations greater than 20 ng/ml. Malignancies associated with these elevations were hepatoma, germ cell tumors, Wilms' tumor, and carcinoma of unknown origin. Carcinoma metastatic to the liver was not associated with AFP elevations. In AFP-associated tumors we found serial measurements of serum AFP to be of value in assessing therapeutic response. Benign diseases associated with AFP elevations included neonatal hepatitis, viral hepatitis, fulminant toxic hepatitis, and cryptogenic cirrhosis.