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

Abstract

We developed a RIA specific for the free beta hCG employing anti-beta hCG monoclonal antibody 1D12. This RIA was highly sensitive to free beta hCG; the minimum detectable concentration was 0.4 ng/ml. alpha hCG, LH, beta LH, and FSH had little effect in the assay; the cross-reactivity of hCG was about 4%. Using this RIA, we measured serum free beta hCG 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 beta hCG was not detected at any time. In contrast, serum free beta hCG was measurable in the majority of patients with trophoblastic disease. Strong correlations were found between the concentration of free beta hCG and that of hCG in each type of trophoblastic diseases. The mean free beta hCG 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 beta hCG to hCG ratio throughout their clinical course. We conclude that the production of free beta hCG increases with the immaturity of the trophoblastic cell, and the degree of differentiation of trophoblastic cells may be reflected by the free beta hCG to hCG ratio.

Are Laboratories Reporting Serum Quantitative hCG Results Correctly?

“…In pregnancy, intact hCG predominates, whereas free hCG␤ accounts for Ͻ1% of total ␤ hCG (hCG ϩ hCG␤) in serum (4,6 ). However, the free hCG␤ concentration in patients with trophoblastic diseases or testicular tumors is disproportionately increased, and the ratio of free hCG␤ to intact hCG or to hCG ϩ hCG␤ is markedly increased (7,8 ). Therefore, measurements of hCG ϩ hCG␤ and free hCG␤ are important in diagnosis and management of trophoblastic diseases and testicular tumors (8 -12 ).…”

Different hCG assays to measure ectopic hCG secretion in bladder carcinoma patients

“…Kit 1 and kit hCG fraction. This is important when evaluating different thCG assays because the free f-subunit and the free fl/t-hCG ratio varied depending on the stage of tumour progression and higher values are associated with malignant and invasive forms of choriocarcinomas (Fan et al, 1987). As shown in Figure 1 and in Table I, the assay measuring both fractions, intact plus nicked hCG, performed better than the assay measuring intact fraction alone.…”

“…The diagnostic sensitivities using t-hCG assays ranged between 63.6% and 75.7%, and was 72.7% using free fl-hCG assay; with i-hCG plus hCGn assay the diagnostic sensitivity obtained was 18.2% and measuring the i-hCG alone the sensitivity was 6%. Table I shows the ratio (%) between free fl-hCG and thCG, according to the different kits (Fan et al, 1987). These ratios ranged between 2.2% and 6.6% (kit 2 and kit 4 respectively).…”

Elevated hCG Outside of Pregnancy—Diagnostic Considerations and Laboratory Evaluation

“…They also found that as trophoblastic diseases became less differentiated and more invasive, there was a corresponding rise in the free ␤-hCG to total hCG ratio. There was also a greater likelihood that free ␤-hCG would be detected in the patient's serum (22,23). Free ␤-hCG thus became a valuable tool in evaluating the possibility of GTN in the setting of unexplained elevated hCG.…”