Specific detection of type II human chorionic gonadotropin beta subunit produced by trophoblastic and neoplastic cells

Abstract

Background: The sequence of the beta-subunit of human chorionic gonadotropin (hCGβ) varies depending on whether hCGβ is encoded by type I or type II genes. Type II genes are upregulated in trophoblast and cancer but hCGβ can be detected in the serum of nonpregnant women and healthy individuals. We aimed to determine whether monoclonal antibody (mAb) FBT11-II specifically detects hCGβ encoded by type II genes (type II hCGβ).

Methods: Competitive inhibition assays with synthetic peptides, immunocytochemical and immunohistochemical studies, type II hCGβ dosing immunoassays and sequencing of CGB genes were performed.

Results: Competitive inhibition assays determined that mAb FBT11-II recognizes the type II hCGβ derived peptide. CGB mRNA sequencing of JEG-3 (trophoblastic) and T24 (bladder) cell lines confirmed that JEG-3 expresses type II genes while T24 expresses exclusively type I. FBT11-II only recognizes JEG-expressed hCGβ. Placenta immunohistochemical studies confirmed that type II hCGβ expression is restricted to the syncytiotrophoblast. Immunoassays detected type II hCGβ in serum of patients with either nontrophoblastic cancers or fetal Down syndrome.

Conclusion: Type II gene expression can be detected using FBT11-II. This specific recognition could improve the clinical usefulness of assays aimed at either managing aggressive tumors or screening for Down syndrome.

Keywords: Cancer; Gene expression; Gonadotropins; Pregnancy.