Molecular forms of human chorionic gonadotropin: characteristics, assays and clinical use - Revista Brasileira de Ginecologia e Obstetrícia

The human chorionic gonadotropin (hCG) results from a non-covalent linkage of two subunits, alpha (alphahCG) and beta (betahCG), separately synthesized by normal trophoblastic tissue, hydatiform mole, choriocarcinoma, pituitary cells, and tumoral tissues of different histologic types. The peptide chain and its further glycosylation in the secretory cell involves the complex action of different enzymes. This complexity results in the secretion of heterogeneous molecular forms. The different molecules might be found in serum, urine and amniotic fluid of pregnant women; serum, urine, and vesicles of patients with hydatiform mole or choriocarcinoma and in other biological fluids of normal non-pregnant women and men or patients with different embryonary types of cancer. Both the intact hCG molecule and its free subunits and the hyperglycosylated (H-hCG), nicked (N-hCG) and core fragment of betahCG (CF- betahCG) variant forms have relevant clinical use. Depending on the prevalent molecular form or the proportion of the variant form to the intact hCG in a determined clinical situation the measurement of a specific molecule is chosen. This review analyzes the clinical use of hCG and its related molecules in the early detection of ectopic pregnancy or patients with higher risk of abortion, in the identification of an embryo or fetus with chromosomal abnormalities, and in the evaluation of risk for preeclampsia or fetal growth restriction. The review also examines the use of hCG and variant forms as tumor markers. It is concluded that it is useful to measure hCG and/or related molecules in clinical practice, but difficulties in developing and achievement of more sensitive and specific new assays limit their use.