Human Chorionic Gonadotropin

Human chorionic gonadotropin is a 38 kD hormone secreted by placental syncytiotrophoblasts, whose function is to maintain the corpus luteum. It consists of two subunits, an a subunit and a P subunit. The a subunit is closely related to the a subunit of anterior pituitary hormones such as luteinizing hormone (LH), follicle-stimulating hormone (FSH), and thyroid-stimulating hormone (TSH). The P subunit is biologically active and structurally and antigenically distinct, allowing for the production of specific antibodies used in immunoassays.9 However, at times, these antibodies may cross-react with the P subunit of LH, which is 70% homologous to that of hCG. In addition, hCG, at high levels, may clinically mimic these pituitary hormones. Hyperthyroidism has been reported,10 and the 5% of GCT patients who develop gynecomastia are believed to do so secondary to a testosterone/estrogen imbalance caused by the effect of hCG on the Leydig's cells.

Tumors, in addition to producing intact hCG subunits, may produce so-called "nicked" free P subunits. These nicked molecules are biologically inactive, lack certain intra-amino acid bonds, and are therefore unstable and can be quickly degraded. The nicked isoforms and degradation products are not recognized by certain immunoassay antibodies and may be a source of false-negative study results or underestimation of the hCG level (Figure 7-3).11

Only minute amounts of hCG (< 5 IU/L) are detectable in healthy adults. Levels of hCG are elevated in pregnancy and in gestational disorders. As well, elevated serum concentrations have been reported in cases of hepatic, pancreatic, gastric, pulmonary, breast, renal, and bladder tumors and in cases of multiple myeloma.4 However, concentrations > 10,000 IU/L are seen only in pregnancy and

Figure 7-2. Yolk-sac tumor with positive AFP immunohistochemical staining. (Note Schiller-Duval body to the left of the image.)

Germs Cells The Gonad
Figure 7-3. Structure of hCG and its breakdown products. (Adapted from Bower M, Rustin GJS. Serum tumor markers and their role in monitoring germ cell cancers of the testis. In: Comprehensive textbook of genitourinary oncology, ed 2. Philadelphia, Lippincott, Williams & Williams 1999: p. 927-8.)

in patients with GCTs, gestational trophoblastic disease, and (rarely) trophoblastic differentiation of lung or gastric primaries.12 Of patients with GCTs, 40 to 60% will have elevated hCG levels; this includes essentially all patients with choriocarci-noma, 80% of patients with embryonal carcinoma, and 10 to 25% of those with seminoma (Figure 7-4).13 Elevated hCG levels imply syncytiotropho-blastic elements, even when these elements cannot be demonstrated histologically.

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