Radioimmunoassay of the Serum Freeβ-Subunit of Human Chorionic Gonadotropin in Trophoblastic Disease*

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Abstract
We developed a RIA specific for the free βhCG employing anti-βhCG monoclonal antibody 1D12. This RIA was highly sensitive to free βhCG; the minimum detectable concentration was 0:4 ng/ml. αhCG, LH, βLH, and FSH had little effect in the assay; the cross-reactivity of hCG was about 4%. Using this RIA, we measured serum free βhCG concentrations in 38 normal pregnant women and 72 untreated patients with 3 types of trophoblastic disease: hydatidiform mole (n = 15), invasive mole (n = 29), and choriocarcinoma (n = 28). All of these samples were simultaneously assayed for hCG by RIA. In normal pregnant women, serum hCG changed as pregnancy progressed, but serum free βhCG was not detected at any time. In contrast, serum free βhCG was measurable in the majority of patients with trophoblastic disease. Strong correlations were found between the concentration of free βhCG arid that of hCG in each type of trophoblastic diseases. The mean free βhCG to hCG ratio was lowest for hydatidiform mole and highest for choriocarcinoma, and the difference between the ratios in these 2 groups was statistically significant. Serial measurements in 7 patients with trophoblastic disease failed to reveal remarkable changes in the free βhCG to hCG ratio throughout their clinical course. We conclude that the production of free βhCG increases with the immaturity of the trophoblastic cell, and the degree of differentiation of trophoblastic cells may be reflected by the free βhCG to hCG ratio.