Radioimmunoassay of free β-subunit of human chorionic gonadotropin as a prognostic test for persistent trophoblastic disease in molar pregnancy

A new radioimmunoassay system was established with a monoclonal antibody (1E5) that distinguishes the free β-subunit of human chorionic gonadotropin in the presence of intact human chorionic gonadotropin, showing only 0.23% cross-reactivity with the intact human chorionic gonadotropin molecule and virtually no cross-reactivity with other glycoprotein hormones or their β-subunits. Serum samples, taken at initial diagnosis from nine patients with hydatidiform mole and spontaneous remission and 12 patients with subsequent progression to persistent trophoblastic disease, were assayed for free and total levels of the β-subunit of human chorionic gonadotropin. The assay results were expressed as a ratio of nanograms of free β-subunit per 1000 mIU of total β-subunit. Eight of nine patients with mole and spontaneous remission had a ratio value <4 whereas 10 of 12 patients with subsequent persistent disease had a ratio value >4. Statistical analysis with γ² showed a highly significant correlation of high ratios with eventual progressive disease (p = 0.0009). This study suggests that excessive production of the free β-subunit of human chorionic gonadotropin may identify patients with a high likelihood of developing persistent trophoblastic disease.