Differences in total human chorionic gonadotropin immunoassay analytical specificity and ability to measure human chorionic gonadotropin in gestational trophoblastic disease and germ cell tumors.

OBJECTIVE: To determine the ability of several radioimmunoassays and commercial two-site immunoassays to detect the first World Health Organization International Reference Reagents (IRRs) for 6 defined human chorionic gonadotropin (hCG) variants and to compare their performance in measuring hCG in sera from patients with gestational trophoblastic disease (GTD) and germ cell tumors (GCTs) of the testis or ovary. STUDY DESIGN: The reactivity of the different assays with the 6 IRRs together with the current fourth International Standard (IS, 75/589) was tested using 5 commercial two-site assays as well as 2 competitive polyclonal radioimmunoassays (RIAs) and a competitive monoclonal immunoassay. Individual samples from 41 patients (19 GCT and 22 GTD) with high circulating levels of hCG (range, 718-6,055,000 IU/L) were diluted and measured using the various immunoassays. RESULTS: The results of 4 GCT patient samples varied markedly among the assays, including 1 sample that was grossly underestimated by 3 of the commercial assays. CONCLUSION: Comparison of each assay's reactivity to the variant isoforms revealed that recognition of the isoforms was highly variable, particularly for hCGbeta and hCGbeta core fragment (hCGbetacf).

Human chorionic gonadotropin free beta-subunit measurement as a marker of placental site trophoblastic tumors.

OBJECTIVE: To evaluate the utility of free human chorionic gonadotropin beta-subunit (hCGbeta) proportion of total hCG measurement to distinguish placental site trophoblastic tumor (PSTT) from more common forms of gestational trophoblastic disease (GTD). STUDY DESIGN: Serum samples collected from PSTT, persistent trophoblastic disease (PTD) and choriocarcinoma patients were used for retrospective analysis of free hCGbeta-subunit. Results were reported as a percentage of total hCG using our in-house competitive radioimmunoassay. RESULTS: The percentage of free hCGbeta was significantly greater in serum from 18 PSTT patients, yielding a median value of 45.5% than in a combined GTD group of 49 PTD and 12 choriocarcinoma patients. Receiver operating characteristic analysis confirms that the percentage free hCGbeta distinguishes PSTT from GTD patients. Choriocarcinoma patients had significantly higher hCGbeta measurements than PTD patients and were not well distinguished from PSTT patients. CONCLUSION: Our findings show that an elevated proportion of free hCGbeta-subunit is a helpful but not definitive test to discriminate PSTT from other forms of GTD.