The ability to reliably detect aberrant glycosylation of
human chorionic gonadotropin (hCG) may have profound implications for the diagnosis and monitoring of malignant
gestational trophoblastic neoplasia,
germ cell tumors, other
malignancies, and
pregnancy complications. To become a clinically useful assay, however, this discrimination of glycoforms should be possible on minimally treated
biological specimens. Towards this end, we have developed a
lectin-based sandwich-type immunoassay to compare the glycosylation patterns of hCG among urine specimens from patients presenting with a normal pregnancy,
invasive mole,
choriocarcinoma, and male
germ cell tumors using
carbohydrate-free
antibody fragments as capture
reagents and a panel of eight
lectins, five recognizing neutral
sugars and three recognizing
sialic acid. There was no significant difference in the binding of any of the
lectins to hCG in the urine of women over the gestational range of 6-38 weeks. Three
lectins, however, exhibited differential binding to urinary hCG derived from these normal pregnant controls and that from patients with malignant forms of
gestational trophoblastic disease and male
germ cell tumors.
Galanthus nivalis agglutinin and Maackia amurensis
lectin, which bind terminal
mannose and alpha(2-3)sialic
acid, respectively, preferentially bound pregnancy-derived hCG, whereas the
lectin, wheat germ agglutinin, which binds
sialic acid and beta(1-4)N-acetylglucosamine, exhibited decreased binding to pregnancy-derived hCG compared to that from patients with male
germ cell tumors and malignant
gestational trophoblastic neoplasia. The differential binding observed with these three promising
lectins is most encouraging and warrants further examination. The experimental paradigm also holds promise for the development of comparable assays for other glycosylated
tumor markers.