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

Abstract

The secretion of human chorionic gonadotropin and its subunits was examined by a heterologous hCG/hCG-beta radioimmunoassay and homologous radioimmunoassays of the alpha- and beta-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-beta (20-286 micrograms/l) and 8 (15%) of hCG-alpha (14-498 micrograms/l). A selective elevation of hCG-subunits without the hormone was never observed. Serum concentrations of hCG-beta were to low to interfere in the heterologous radioimmunoassay using 125I-hCG and anti-hCG-beta 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-beta (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-alpha between patients with testicular cancer (hCG:2-82%; mean, 22%; n = 7; hCG-alpha: 11-61%; mean, 31%; n = 7) and pregnant women (hCG: 0%; n = 3; hCG-alpha: 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 beta-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-alpha indicate structural variations in the carbohydrate chains. It is assumed that Con A nonreactive hCG and hCG-alpha 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.