Enzyme Immunoassay of Urinary -Core Fragment of Human Chorionic Gonadotropin as a Tumor Marker for Ovarian Cancer

Human chorionic gonadotropin (hCG), a glycoprotein hormone composed of two nonidentical α- and β-subunits, is normally produced by trophoblasts. Serum and urine from some patients with nontrophoblastic tumors are found to contain similar immunoactivity to the β-subunit of hCG and this phenomenon has been recognized as an ectopic hCGβ production ( 1 ). Elevated levels of ectopic hCGβ are detected more frequently in urine than in serum. Recent studies have shown that urinary ectopic hCGβ mainly represents hCGβ-core fragment (β-CF) ( 2 ). Urinary β-CF consists of residues 6-40 disulfide bridged to residues 55-92 of the β-subunit of hCG ( 3 , 4 ), suggesting that it may be a degradative product of hCGβ. Such partial identity of the amino acid sequence between intact hCG, free hCGβ, and β-CF makes their specific measurements difficult. The existence of two more antigenic sites unique to hCGβ has been demonstrated. The one domain locates in the β-core portion and the other in COOH- terminal region of the β-subunit of hCG Fig. 1 ). By selecting appropriate pairs of antibodies to construct sandwich enzyme immunoassays (EIAs), it is possible to design methods that measure either intact hCG, free hCGβ, or β-CF Table 1 ). By using this EIA, the authors assessed the clinical usefulness of urinary β-CF as a tumor marker for nontrophoblastic tumors ( 5 , 6 ). Here, the authors describe the methods to measure urinary β-CF in patients with ovarian cancer.

---

	First antibody	Second antibody			Cross-reactivity (%)
						Sensitivity	Intact	Free
Assay	Code	Epitope	Code	Epitope	Specificity	(ng/ml)	hCG	hCGβ	β-CF
EIA-1	No.277(MoAb)	β-CTP	No.224(MoAb)	hcGa	Intact hCG	0.01	100	15	1.0
EIA-2	No.209(MoAb)	hCGβ	No.115(PoAb)	β-core	Free hCGβ	0.01	1.9	100	1.9
EIA-3	No.229(MoAb)	β-core	No.105(PoAb)	β-core	β-CF	0.01	3.3	100	100