Immunological recognition and clinical significance of nicked human chorionic gonadotropin in testicular cancer

Abstract

We studied the physical properties, immunological recognition, and clinical significance of nicked human chorionic gonadotropin (hCGn) in testicular cancer. Upon sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing conditions, the β-subunit of hCGn (hCGβn) dissociated into two peptides, and, by reversed-phase chromatography, hCGβn was found to be less hydrophobic than hCGβ. Immunologically, hCGn lacked two epitopes specific for holo-hCG (c1, c2), whereas at least five hCGβ epitopes (β1-β5) were preserved, and, as a result, recognition of hCGn by different hCG assays varied widely. In 309 sera and 88 urine samples from patients with seminomatous or nonseminomatous testicular cancer, hCG-only, hCG + hCGn, and hCG + hCGn + hCGβ + hCGβn + hCGβ core-fragment assays gave parallel results. hCGn was more abundant in urine than in serum samples. In conclusion, hCGn lacks two conformationally dependent epitopes of hCG, causing a change in hydrophobicity and explaining its failure to react in certain holo-hCG assays. Recognition of hCGn, however, does not seem to be crucial in the routine use of serum hCG as a tumor marker in patients with testicular cancer.