Histological origins of discordant chorionic gonadotropin secretion in malignancy

Serum hCG, alpha hCG, and beta hCG levels were measured using monoclonal antibodies in women with trophoblastic disease (n = 138) and germ cell neoplasia (n = 123). Elevated serum beta hCG levels were present initially in the majority of the trophoblastic disease patients. By 12 weeks postevacuation raised serum beta hCG levels were detected in 42% of patients with malignant disease compared to 12% of patients with benign disease. No significant relationship was found between the initial alpha hCG levels and malignancy or resistance to chemotherapy. Increased serum free subunit levels did not distinguish between choriocarcinoma or benign hydatidiform moles, but increasing beta hCG to hCG ratios identified patients with high risk disease requiring multiagent chemotherapy. In nongestational malignancy, increased subunit levels occurred in fewer patients and to a lesser extent. Higher beta hCG and alpha hCG levels coincided with a histology of proliferating intermediate and cytotrophoblast cells, respectively, while high hCG levels occurred in association with syncytial proliferation. A histological mechanism for hCG synthesis is proposed, whereby mRNA for hCG subunits in syncytium depends on supplies of presynthesized mRNA introduced by fusion from differentiating cytotrophoblasts. Abnormalities in the extent and rate of differentiation would result in imbalanced subunit secretion.