Can the Same hCG Assay be Used as a Tumor Marker and for Pregnancy?

The answer lies within the specificity profiles and epitopes recognized by diagnostically relevant antibodies (Abs) directed against human chorionic gonadotropin (hCG). This provides the basis for improving the measurement of hCG by the harmonization of epitopes of the Abs used and to build broad assay specificity consensus for use as a tumor marker, pregnancy and pregnancy- related disorders.

Work done by eight companies and research groups submitted 69 Abs directed to hCG and hCG-related variants. Each of these Abs were characterized in detail by the participants of the Second International Workshop (WS) on hCG of the International Society of Oncology and Biomarkers Tissue Differentiation 7 (ISOBM TD-7).

To determine the specificities of the Abs, the First WHO International Reference Reagents for six hCG variants, hCG, hCGn, hCGβ, hCGβn, hCGβcf, and hCGα (http://www.nibsc.org/) were used along with seventeen reference monoclonal (m)Abs  with defined epitopes.

The data shows that 48 mAbs recognized hCGβ, 8 hCGα-, and 13 αβ-heterodimer-specific epitopes. Twenty-seven mAbs were of pan hCG specificity. Two of these pan hCG mAbs had very low cross-reactivity with hLH (<0.1 %; epitope β₁), 12 with low hLH cross-reactivity (<1.0 %; epitopes β_2/4), and 13 with high hLH cross-reactivity (>>1 %; epitopes β_3/5). Four mAbs recognized epitopes on hCGβcf-only (e.g., epitopes β₁₁ and β₁₃) and six mAb epitopes on the remote hCGβ-carboxyl-terminal peptide (epitopes β₈ and β₉).

Sandwich assays used for both a tumor marker and for pregnancy should measure hCG, hCGβ and hCGβcf. This type of assay should recognize the protein backbone of the analytes preferably on an equimolar basis, should not cross-react with hLH, and should not result in a decrease in signal by missing the detection of the hCGβcf. Such assays can be constructed using pairs of mAbs directed against the cystine knot-associated epitope β1 in combination with epitopes β2 or β4 on hCG peptide loops1+3 protruding from the central cysteine knot.

So the answer to the question is, “yes”. The same hCG assay can be used as a tumor marker and for pregnancy.

References
P. Berger, E. Paus, P. M. Hemken, C. Sturgeon, W. W. Stewart, J. P. Skinner, L. C. Harwick, S. C. Saldana, C. S. Ramsay, K. R. Rupprecht, K. H. Olsen, J.-M. Bidart, U.-H. Stenman. Candidate epitopes for measurement of hCG and related molecules: the second ISOBM TD-7 workshop. Tumor Biol. 2013; 34:4033-4057.

P. Berger, C. Sturgeon, J.-M. Bidart, E. Paus, R. Gerth, M. Niang, A. Bristow, S. Birken, U.-H. Stenman. The ISOBM TD-7 workshop on hCG and related molecules. Towards user-oriented standardization of pregnancy and tumor diagnosis: assignment of epitopes to the three-dimensional structure of diagnostically and commercially relevant monoclonal antibodies directed against human chorionic gonadotropin and derivatives. Tumor Biol. 2002; 23:1–38.