Serum alpha-fetoprotein levels in human disease: perspective from a highly specific monoclonal radioimmunoassay.

Abstract

A rapid, multisite radioimmunoassay for measurement of human .alpha.-fetoprotein (AFP) that uses 2 high-affinity monoclonal antibodies directed against distinct and separate determinants on the protein was developed and designated M-RIA. The sensitivity of the simultaneous-sandwich M-RIA is .apprxeq. 0.5 ng/ml of serum after 1-h incubation. Serum AFP levels were measured in 1747 individuals with hepatocellular carcinoma (HCC), acute and chronic hepatitis B virus infection, chronic hepatitis B surface antigen (HBsAg)-carrier states, cirrhosis, other malignant tumors and normal and disease controls to determine the specificity of the assay. Of patients with HBsAg-positive HCC, 80% (68/85) had AFP levels of > 200 ng/ml (range, 260 to > 200,000 ng/ml). All 450 normal subjects and 477 chronic HBsAg-positive carriers had levels of < 20 ng/ml. In acute and chronic hepatitis B, cirrhosis and other malignant tumors and in the remaining disease controls, AFP levels were < 20 ng/ml in 99.3% of the subjects, the great majority (> 96%) being < 5 ng/ml. Only 2 of 1635 individuals, one with acute hepatitis and the other with carcinoma of the esophagus, had AFP levels of > 100 ng/ml. These observations are at variance with previous studies with conventional polyvalent RIA of AFP levels of > 20 ng/ml in .apprxeq. 40% of acute and chronic hepatitis and in 30% of cirrhosis. This striking specificity of the M-RIA is probably due in part to recognition of epitopes unique to AFP and suggest that such an assay may be used in the detection, early identification and monitoring of AFP-producing tumors in high-risk populations.