Selecting an appropriate hCG test for managing gestational trophoblastic disease and cancer

Human chorionic gonadotropin (hCG) is a glycoprotein composed of 2 dissimilar subunits, alpha and beta, joined non-covalently. This hormone is not only heterogeneous in peptide structure but also in combination of subunits and in the structure Of carbohydrate side chains. Common hCG-related molecules in serum samples include regular hCG, hyperglycosylated hCG (ITA), nicked hCG, nicked ITA, hCG missing the beta-subunit C-terminal extension, free alpha-subunit, free beta-subunit, free beta-subunit missing the C-terminal extension, hyperglycosylated free beta-subunit and nicked free beta-subunit. The same molecules plus beta-core fragment are present in urine samples. While ITA and regular hCG predominate in pregnancy samples, any one of these multiple hCG-related molecules may be the principal source of immunoreactivity in gestational trophoblastic disease, gestational trophoblastic neoplasm, choriocarcinoma and placental site tumor cases as well as in testicular cancer and germ cell tumor. As such it is critical to appropriately detect all these isoforms in the management of these diseases. Only 2 tests, the DPC Immulite (DPC, Inc., Los Angeles, California) and U.K. RIA (radioimmunoassay) (used at Charing Cross Hospital, London) appropriately detect all these hCG-related molecules. False positive hCG results are a major problem in the management of gestational trophoblastic disease and cancer. A particular problem is observed with the Abbott AxSym test. This test is flawed in design. It should be avoided in the management of gestational trophoblastic disease and cancer. As shown in a blind study, a proportion of false positive samples in the Abbott AxSym test (Abbott Laboratories, Inc., Chicago, Illinois) can also be false positive with the U.K. RIA; none are false positive with the DPC Immulite test. Results clearly show that the DPC Immulite/Immulite 2000 is the only appropriate assay for monitoring patients with gestational trophoblastic disease or cancer.