Immunoreactive human chorionic gonadotropin and its free ß-subunit in serum and ascites of patients with malignant tumors

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-ß)] was found to be elevated above the
reference value (>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-ß) 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-ß 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-ß 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-ß 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-ß
immunoreactivity. Incubation experiments of purified holo-hCG in
ascites for 24 h at -20, 20, or 37°C showed no substantial
dissociation of the hCG molecule and release of free hCG-ß
immunoreactivity, thus arguing against production of free hCG-ß by
degradation of holo-hCG and in favor of its tumor-related
secretion. In conclusion, hCG-ß immunoreactivity is frequently
elevated in malignancy-related ascites and appears to be related to
the presence of free ß subunit of hCG rather than that of the
intact hCG molecule. Interestingly, hCG-ß determination in ascites
proved to be clearly superior to serum measurement in
discriminating between tumor and cirrhosis. Thus, hCG-ß might be a
useful marker of malignancy-related ascites and should be
prospectively assessed for possible clinical use in comparison with
other well-established parameters, such as cytology and protein
determination. For this purpose, according to our results, only
assays that exhibit a high sensitivity for free hCG-ß subunit
appear to be suitable.