Human chorionic gonadotropin (hCG) is a specific
tumor marker glycoprotein hormone for trophoblastic diseases. It contains 4
asparagine-linked and 4
serine-linked
carbohydrate units. Recently, variations in the
carbohydrate moieties of hCG in chorio-
carcinoma have been suggested. However, the immunological method of detecting these malignant transformational changes of
carbohydrate units in hCG have not been investigated. We therefore attempted to assess the possibility of establishing a radioimmunoassay system which can detect these transformational changes in
serine-O-glycosidically linked
carbohydrate units of hCG. HCG-specific
hCG beta COOH-terminal portion contains all 4 O-glycosidically linked
sugar chains (positions 121, 127, 132 and 138). An antiserum (R141) generated against the enzymatically cleaved,
desialylated hCG beta COOH-terminal
peptide (residue 123-145) by toepad immunization method was extensively characterized. This antiserum reacts with
asialo-hCG better than with native hCG. It does not bind with synthetic COOH-terminal
peptides nor
monosaccharides such as
N-acetyl-D-galactosamine and
D-galactose, which are
sugar components in O-glycosidic
carbohydrate chains. The HF-treated
asialo-hCG, in which
galactose residues are further removed, still reacts with the antiserum. The antiserum requires both the
peptide sequence and
N-acetyl-D-galactosamine residues for its binding. Glycophorine and
fetuin, which also contain the same O-glycosidic
carbohydrate structure, do not react with the antiserum. Beta subunit gains its binding capability to the antiserum only upon desialylation, while native alpha and beta subunits do not react. The antiserum has high specificity toward
asialo-hCG in which particularly O-glycosidic
carbohydrate units are desialylated. With a specific radioimmunoassay system using this antiserum (R141), urinary hCG preparations from 29 patients with various trophoblastic diseases were analyzed.
Asialo-hCG immunoactivity was insignificant in all patients with
hydatidiform mole, invasive hydatidiform mole and persisted trophoblastic disease. However,
asialo-hCG was found in 2 out of 6 cases of
choriocarcinoma. The existence of
asialo-hCG may be related to the advancement of disease.(ABSTRACT TRUNCATED AT 400 WORDS)