Human chorionic gonadotropin (hCG) and its free subunits in hydrocele fluids and neoplastic tissue of testicular cancer patients: insights into the in vivo hCG-secretion pattern.

To obtain insight into the secretion pattern of human chorionic gonadotropin (hCG) and its free subunits, hCG alpha and hCG beta, in vivo, we analyzed hydrocele fluids of 13 patients with testicular cancer and correlated the respective values to those of cubital vein and testicular vein serum. As a control population, patients with nonmalignant hydroceles (n = 11) were studied. Analyses were performed with a set of highly sensitive and specific time-resolved fluoroimmunoassays based on our own panel of monoclonal antibodies. In the collective of testicular cancer patients, increased hydrocele levels of either hCG or free hCG alpha or free hCG beta were observed in 77, 54, and 92% of cases; the corresponding percentages for cubital vein serum were 62, 23, and 31%. The cubital vein ratio of hCG:hCG alpha (546:1) and hCG:hCG beta (51:1) decreased to 64:1 and to 7:1 in the hydrocele fluids. Surprisingly, hydrocele fluids of five patients with pure seminoma, who were negative for the three markers in the periphery, revealed an elevation of free hCG beta in all cases, while hCG alpha and holo-hCG were elevated twice. Final proof that hCG beta and hCG alpha are indeed produced by these previously termed "marker negative" seminomas has been achieved by reverse transcriptase-polymerase chain reaction with primers specific for the alpha-subunit and the four most abundantly transcribed hCG beta genes 3, 5, 7, and 8. From these data, we conclude that: (alpha) seminomatous and nonseminomatous testicular cancers, irrespective of histology, secrete hCG and its free subunits; (b) the amount of free subunits being secreted in vivo by these tumors has been underestimated; and (c) the classification in marker-positive and marker-negative testicular cancer should be reconsidered.