Molecular heterogeneity of human chorionic gonadotropin and its subunits in testicular cancer

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Abstract
The secretion of human chorionic gonadotropin and its subunits was examined by a heterologous hCG/hCG-β radioimmunoassay and homologous radioimmunoassays of the α- and β-subunit in patients with nonseminomatous testicular germ cell tumors. Of 53 patients, 32 (60%) had elevated levels of hCG (9 IU/l-4.5 million IU/l), 12 (23%) elevated serum concentrations of hCG-β (20–286 μg/l) and 8(15%) of hCG-α (14–498 μg/l). A selective elevation of hCG-subunits without the hormone was never observed. Serum concentrations of hCG-β were to low to interfere in the heterologous radioimmunoassay using 125I-hCG and anti-hCG-β antiserum. Gelfiltration of patient's sera (n = 5) on Ultrogel AcA 44 column confirmed the secretion of free subunits and additionally a high molecular form of hCG-β (70,000) in three of five serum specimens. Furthermore, the molecular heterogeneity of hCG and hCG-subunits was examined by affinity chromatography on Concanavalin A (Con A)-sepharose. There was a significant difference of Con A nonreactive hCG and hCG-α between patients with testicular cancer (hCG: 2–82%; mean, 22%; n = 7; hCG-α: 11–61%; mean, 31%; n = 7) and pregnant women (hCG: 0%; n = 3; hCG-α: 0–13%; mean, 6%; n = 5). Con A nonreactive and reactive hCG of patients with cancer revealed similar binding in a radioreceptor gonadotropin assay. The Con A nonreactive fraction of the β-subunit was determined to be 20–73% (mean, 50%; n = 6) in serum samples of patients with testicular cancer and did not differ from the percentage in pregnant women (29–67%; mean, 46%; n = 4). The lectin binding heterogeneity of hCG and hCG-α indicate structural variations in the carbohydrate chains. It is assumed that Con A nonreactive hCG and hCG-α are directly liberated by nonsecretory mechanism from tumor cells into the circulation. Determination of hCG released by cell damage may have clinical significance in patients with testicular cancer under chemotherapy.