Molecular heterogeneity of hCGbeta--related glycoproteins and the clinical relevance in trophoblastic and non-trophoblastic tumors

Abstract

We analyzed immunoreactive hCG/hCGbeta (IR-beta) in the sera and urine of patients with trophoblastic diseases and non-trophoblastic tumors by using enzyme immunoassays (EIAs) specific for intact hCG, free hCG beta, and beta-core fragment of hCG (beta-CF). In trophoblastic diseases, while intact hCG and free hCGbeta were contained in both serum and urine, the beta-CF could be detected only in the urine of the patients. The relative contribution of the beta-CF to the total urinary IR-beta accounted for about 30-50% in normal early pregnancy and hydatidiform mole, and more than 60% in choriocarcinoma. We conclude that intact hCG should be measured in the serum rather than in the urine as a tumor marker for trophoblastic diseases, and suggested that the ratios of intact hCG, free hCGbeta, and beta-CF to each other may be useful indices in the differential diagnosis of trophoblastic diseases. Ectopic IR-beta was also investigated in the sera and urine of the patients with cervical, endometrial, ovarian, lung, and bladder carcinomas. We found that even when IR-beta could not be detected in the serum, the urine of the same patients with cancer often contained the significant amounts of IR-beta. The chromatographic study indicated that these urinary IR-beta were essentially attributed to beta-CF, leading to the evaluation of urinary beta-CF as a tumor marker. The positive rated of urinary beta-CF were 48% for cervical, 38% for endometrial, and 84% for ovarian, 40% for lung, and 42% for bladder carcinomas. We conclude that ectopic production of hCG beta by non-trophoblastic tumors is not a rare phenomenon and it can be recognized as a tumor marker when beta -CF is measured in urine of the patients.