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

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. Fig. 1. Two antigenic sites: the first domain is located in the β-core portion and the second domain is located in the COOH-terminal region of the β-subunit of hCG. Table 1Specificities and Sensitivities of Enzyme-Immunoassays Specific for Intact hCG(EIA-1), Free hCGβ(EIA-2), and β-CF(EIA-3)

First antibody

Second antibody

Cross-reactivity (%)

Sensitivity

Intact

Free

Assay

Code

Epitope

Code

Epitope

Specificity

(ng/ml)

hCG

hCGβ

β-CF

MoAb: monoclonal antibody. PoAb: polyclonal antibody.

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