Human placental and pituitary glycoprotein hormones and their subunits as tumor markers: A quantitative assessment

With the use of subunit immunoassays that also measured high concentrations of complete glycoprotein hormones, the common α-subunits and β-subunits of chorionic gonadotropin (CG-β), luteinizing hormone (LH-β), follicle-stimulating hormone (FSH-β), and thyroid-stimulating hormone (TSH-β) were retrospectively determined in sera from 532 patients with lung cancer, gastrointestinal cancer, carcinoid, and islet cell malignant disease and from 299 healthy controls and 280 patients with nonmalignant diseases. Nonparametric statistical methods were used to establish sex-specific 50th, 90th, 95th, and 99th percentile cutoff values for each assay in the major diagnostic subgroups. Values of the α-subunit and CG-β were significantly higher in cancer patients than in healthy controls and patients with appropriately matched nonmalignant diseases, but similar elevations of FSH-β and TSH-β were not observed. LH-β elevations were almost always attributable to cross-reaction with high levels of CG-β. The α-subunit levels exceeded the 95th percentiles of appropriate control populations in 11% of men with lung cancer, 32% of men with gastrointestinal cancer, 50% of men with carcinoid, and 61% of men with islet cell cancer; the corresponding figures for women were 16, 18, 13, and 38%, respectively. Likewise, CG-β exceeded the 95th percentiles of appropriate control populations in 41% of men with lung cancer, 28% of men with gastrointestinal cancer, 0% of men with carcinoid, and 6% of men with islet cell cancer; the corresponding percentages for women were 16, 24, 50, and 19%, respectively. When both tests were used together, with a patient regarded as positive if either α-levels or CG-β levels were elevated, the positive percentages in men rose to 45% for lung cancer, 48% for gastrointestinal cancer, 50% for carcinoid, and 61% for islet cell cancer; the corresponding figures for women were 29, 41, 50, and 43%, respectively. In most cancer patients, elevated α-levels or CG-β values were not accounted for by cross-reaction of complete pituitary gonadotropins; in a few instances, subunit elevations might have been due to primary gonadal failure. Thus the secretion of α-subunit and CG-β far exceeded that of putiutary β-subunits, demonstrating that ectopic secretion of even closely related peptides is a selective process. Both α-subunit and CG-β, especially when used in combination, were potentially useful markers for certain malignant neoplasms; however, their actual clinical utility remains to be established in prospective studies.