Vol. 20 • Issue 1 • Page 44
Human chorionic gonadotropin (hCG)-a protein hormone that stimulates progesterone secretion and appears in biological fluids as intact hCG, free α subunit, free β subunit and various fragments-has been in use as a marker for abnormal pregnancies and malignancies for about 40 years, says David G. Grenache, PhD, associate professor of Pathology and medical director, Special Chemistry Lab, ARUP.
hCG tests are cleared by the FDA for detection of pregnancy only. Dr. Grenache says this is because manufacturers have approached the FDA with data to support use of hCG for pregnancy as opposed to diagnosis/management of specific malignancies.
“I don’t see it changing unless an IVD company decides to submit data to support that claim because they’re going to sell their hCG regardless of whether they have the claim,” Dr. Grenache says. “Physicians still use hCG tests off-label for oncology applications.”
In normal, intrauterine pregnancies, hCG levels rise throughout pregnancy. On average, hCG serum concentrations double approximately every two days, Dr. Grenache says. In an ectopic pregnancy-one in which the blastocysts (a cluster of cells containing an embryoblast that form the embryo) implant outside the uterus-rise of hCG in serum is usually slower than an interuterine pregnancy.
“All by itself, a prolonged doubling time is inadequately sensitive, so you have to combine serial measurements of hCG with transvaginal ultrasound, which would be used to actually visualize the gestational sac in the uterus,” Dr. Grenache says.
Gestational trophoblastic diseases (GTD), an umbrella for partial and complete molar pregnancies and other related diseases, produce hCG so elevated concentrations can serve as a useful tumor marker at diagnosis. A complete molar pregnancy occurs when the sperm duplicates because the nucleus of an egg is lost or inactivated and is apparent by absence of a fetus, placenta, fluid or amniotic membranes. Partial molar pregnancy often happens when two sperm fertilize the same egg; partial placentas, membranes or even a fetus present in a partial mole. Neither type of pregnancy yields a viable fetus.
“A diagnosis of a molar pregnancy would be based upon the clinical signs and symptoms, not just on hCG concentration,” Dr. Grenache says. “Some of the signs and symptoms would be a larger-than-usual uterus [and] the absence of any fetal heart tones in a woman who appears to be pregnant and has elevated hCG. Then ultrasound can be done, and you can see this accumulation of placental-like tissue in the uterus, but there’s no fetus. hCG is one of many tools used. All by itself, it’s not diagnostic.”
If/when molar or ectopic pregnancies are removed, hCG can help monitor therapy response. After removal of the mole, hCG concentration should begin to fall until it is undetectable.
“If the hCG level starts to rise, it indicates there’s still trophoblastic tissue present that hasn’t been removed by surgery or killed by chemotherapy,” Dr. Grenache says. “So it’s used as a surveillance tool.”
hCG is also a useful marker for germ cell tumors, derived from germ cells, making up the ovaries and testes. Since Dr. Grenache says 90% of testicular tumors are germ cell tumors (mostly malignant), while only 20% of ovarian tumors are germ cell tumors (mostly benign), hCG is especially helpful for testicular tumors.
“hCG can be useful as part of the differential diagnosis and in monitoring response to therapy and in a surveillance, just like it is used with GTD,” he says.
Because hCG assays are used for oncology purposes, laboratorians must know the assay’s analytical specificity. “It’s important that an assay be capable of detecting more than just the intact form of the hormone because there are some malignancies that produce only the β subunit of hCG,” Dr. Grenache says.
Dr. Grenache and researchers published a study in 2010 on analytic specificity of eight hCG assays-about 80% of the hCG assays available in the U.S. (from Abbott Laboratories, Beckman Coulter, Ortho Clinical Diagnostics, Roche Diagnostics, Siemens Healthcare Diagnostics and Tosoh Bioscience)-along with hCG variants that the assays can detect. The study concludes that hCG assay manufacturers should indicate the variant specificity of their reagent systems.1
Jill Hoffman is senior associate editor.
1. Whittington J, Fantz CR, Gronowski AM, et al. The analytical specificity of human chorionic gonadotropin assays determined using WHO International Reference Reagents. Clinica Chimica Acta 2010;411:81-5; doi:10.1016/j.cca.2009.10.009.
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