Human chorionic gonadotropin (hCG) is a clinically relevant marker of trophoblastic and nontrophoblastic
malignancies. In the present studies, in addition to determining serum hCG, we investigated the presence and properties of hCG immunoreactivity in
ascites of patients with nontrophoblastic malignant
tumors and, for comparison, in
ascites caused by cirrhotic
liver disease. Total hCG immunoreactivity [hCG (+
hCG-beta)] was found to be elevated above the reference value (greater than 5 IU/liter) in the serum of 2 of 20 patients with
cirrhosis and 11 of 20 patients with malignant
tumors. For comparison, in
ascites, hCG (+
hCG-beta) concentrations were frequently higher than in the corresponding serum samples and exceeded 10 IU/liter in 0 of 20 cirrhotic samples and in 16 of 20 malignant samples. In order to elucidate the nature of the hCG immunoreactive material, all samples were then assessed by immunoradiometric assays specific for the intact hCG molecule (holo-hCG) and the free
hCG-beta subunit, respectively. In the holo-hCG assay, elevated values were detected in 0 of 20 (0 of 20) cirrhotic
ascites (serum) samples and 0 of 20 (1 of 20) malignant
ascites (serum) samples. In the free
hCG-beta assay, on the other hand, no positive results were obtained in the
ascites or serum of 20 patients with
liver cirrhosis; however, 8 of 20 serum samples and 16 of 20
ascites samples derived from
tumor patients were positive. In accord with the immunological data, gel chromatographical studies of malignant
ascites revealed the abundance of free
hCG-beta subunit rather than that of holo-hCG. In contrast to
malignancy-related
ascites, in
ascites of patients receiving hCG
injections for treatment of
infertility, holo-hCG was more abundant than free
hCG-beta immunoreactivity. Incubation experiments of purified holo-hCG in
ascites for 24 h at -20, 20, or 37 degrees C showed no substantial dissociation of the hCG molecule and release of free
hCG-beta immunoreactivity, thus arguing against production of free
hCG-beta by degradation of holo-hCG and in favor of its
tumor-related secretion. In conclusion,
hCG-beta immunoreactivity is frequently elevated in
malignancy-related
ascites and appears to be related to the presence of free beta subunit of hCG rather than that of the intact hCG molecule. Interestingly,
hCG-beta determination in
ascites proved to be clearly superior to serum measurement in discriminating between
tumor and
cirrhosis.(ABSTRACT TRUNCATED AT 400 WORDS)