Molecular heterogeneity of hCG β - related glycoproteins and the clinical relevance in trophoblastic and non-trophoblastic tumors.

We analyzed immunoreactive hCG/hCG β (IR-β) 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 β, and β-core fragment of hCG (β-CF). In trophoblastic diseases, while intact hCG and free hCG β were contained in both serum and urine, the β-CF could be detected only in the urine of the patients. The relative contribution of the β-CF to the total urinary IR-β 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 dieseases, and suggested that the ratios of intact hCG, free hCG β, and β-CF to each other may be useful indices in the differential diagnosis of trophoblastic diseases. Ectopic IR-β 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-β could not be detected in the serum, the urine of the same patients with cancer often contained the significant amounts of IR-β. The chromatographic study indicated that these urinary IR-β were essentially attributed to β-CF, leading to the evaluation of urinary β-CF as a tumor marker. The positive rated of urinary β-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 β by non-trophoblastic tumors is not a rare phenomenon and it can be recognized as a tumor marker when β-CF is measured in urine of the patients.