Hyperglycosylated Human Chorionic Gonadotropin in Serum of Testicular Cancer Patients

Abstract

BACKGROUND Hyperglycosylated human chorionic gonadotropin (hCG-h) contains larger and more complex carbohydrate chains than regular human chorionic gonadotropin (hCG). hCG-h is thought to be the major form of hCG produced by testicular cancers and it has been suggested to play a key role in tumor invasion, but studies on hCG-h in testicular cancer are limited. We studied whether serum hCG is hyperglycosylated, and whether measurement of hCG-h in serum offers clinical value in the management of testicular cancer. METHODS We determined the serum concentrations of hCG-h, hCG, and the free β subunit of hCG (hCGβ) by time-resolved immunofluorometric assays in 176 serum samples (preoperative n = 67, relapse n = 20, follow-up n = 89) obtained from 84 testicular cancer patients. We analyzed the association between preoperative serum concentrations of hCG, hCG-h, and hCGβ with known prognostic factors and progression-free survival time. RESULTS A major proportion of hCG was hyperglycosylated preoperatively, at relapse, and shortly after treatment. The serum concentrations of hCG-h and hCG correlated strongly with each other and had similar diagnostic value. The preoperative serum concentration of hCG-h correlated with prognostic factors and outcome in the same way as hCG. Increased preoperative hCGβ concentration predicted shorter progression-free survival. CONCLUSIONS Most of the hCG expressed by testicular cancers is hyperglycosylated and therefore it is important that hCG assays used for management of testicular cancer recognize hCG-h.

Biomarker development, from bench to bedside

“…hCG-h has been found to be a major form of hCG in nonseminomatous germ cell tumors (NSGCT). hCG-h has been associated with aggressive forms of this disease 132 but it does not add diagnostic or prognostic value additional to that of conventional hCG assays 131 . In 78% of patients with NSGTC, hCGb and hCG were simultaneously elevated but in seminoma, hCG was elevated in only 17%, while hCGb was elevated in 52% of the cases 133 .…”

“…There is no standard for hCG-h but it is presently defined as hCG reacting with B152. Our group is currently using hCG produced by the choriocarcinoma cell line JEG as a temporary standard, in which the content of hCG-h is determined on the basis of the hCG concentration measured by the Wallac assay for intact hCG 131 .…”

Advanced testicular cancer in a society of racial and socio-economic health disparity

“…However, β-HCG levels also may be elevated in patients with non-seminomatous germ cell tumours (NSGCT), such as choriocarcinomas, which are characterised by the presence of both syncytiotrophoblasts and cytotrophoblasts 6. Recent studies by Stenman and coworkers7 show that the hyperglycosylated form of β-hCG is the predominant form of hCG found preoperatively and after relapse and may be a predictor of progression free survival. The α-fetoprotein level is almost never elevated in pure seminomas, but it is elevated in 50–60% of NSGCT 8.…”

Novel tumor markers in the serum of testicular germ cell cancer patients: a review

“…36 Lempiäinen et al showed that a major proportion of HCG was hyperglycosylated preoperatively, at relapse, and shortly after treatment. 36 The serum concentrations of HCG-h and HCG correlated strongly with each other and had similar diagnostic value. HCG-h does not appear to provide clinical information additional to that obtained by conventional HCG assays.…”

“…HCG-h does not appear to provide clinical information additional to that obtained by conventional HCG assays. 36 …”