The diagnostic value of elevated
human chorionic gonadotropin (hCG) and its free alpha (
hCG alpha) and beta (
hCG beta) subunit serum levels as specific
tumor markers for nongonadal
malignancies is controversial. In the present report, different monoclonal based immunoradiometric assays specific for hCG and its free
hCG alpha and
hCG beta subunits have been used to reevaluate the presence of these molecules in the serum of patients with a wide variety of
tumors. Serum samples from patients with newly diagnosed, persistent, or recurrent
malignancies of either known (n = 717) or unknown (n = 32) primary site, healthy blood donors (n = 309), and nonmalignant disease controls (n = 86) were studied using four highly specific and sensitive monoclonal based immunoradiometric assays to hCG and its free subunits. Low level hCG elevations (less than 1000 pg/ml) were found to be common in
cancer patients, normal subjects, and disease controls. However, serum levels greater than 1000 pg/ml were highly diagnostic of gonadal
tumors and specifically identified nonseminomatous
testicular tumors. Significant serum elevations of free
hCG alpha subunit (as high as 3000 pg/ml) were found in approximately 96% of
cancer patients, normal individuals, and disease controls. In contrast, free
hCG beta subunit levels (greater than or equal to 100 pg/ml) were detected in 70 and 50% of patients with nonseminomatous and seminomatous
testicular cancers, respectively, and in 47% of bladder, 32% of pancreatic, and 30% of cervical
carcinomas. All normal subjects and disease controls had free
hCG beta levels less than 100 pg/ml. Thus, the detection of the free
hCG beta subunit in serum of nonpregnant subjects was highly diagnostic of
malignancy in general and specifically defines a subgroup of aggressive nongonadal
malignancies.