Abstract
Objectives
We tested the hypothesis that the free-β subunit (βhCG) is diagnostically more sensitive with total hCG assays (hCGt) not detecting all tumours secreting βhCG. The effects of sex, age, and renal failure were investigated as secondary objectives.
Methods
We compared βhCG with hCGt in 204 testicular cancer patients (99 seminomas, 105 non-seminonatous germ cell tumours). The effects of sex and age were determined in 125 male and 138 female controls and that of renal failure was investigated in 119 haemodialysis patients. Biochemical assessment of gonadal status was performed with LH, FSH, oestradiol and testosterone.
Results
Discordant results were common with isolated increases of hCGt observed in 32 (15.7 %) and βhCG in 14 (6.9 %) patients. Primary hypogonadism was the most common cause of isolated hCGt increases. After therapeutic interventions βhCG decreased below its upper reference more rapidly than hCGt. We observed unequivocal false negative results in two patients with non-seminomatous germ cell tumours. Both occurred in patients with clinical tumour recurrences; in one instance we observed a false negative hCGt while in the second false negative βhCG’s were documented in serial samples.
Conclusions
The similar false negative rates did not support the hypothesis that βhCG will detect more patients with testicular cancer than hCGt. In contrast to hCGt, βhCG was unaffected by primary hypogonadism which is a predictably frequent complication in testicular cancer patients. We therefore recommend βhCG as the preferred biomarker in testicular cancer.
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Research funding: None declared.
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Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
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Competing interests: Authors state no conflict of interest.
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Informed consent: Not applicable.
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Ethical approval: The local Institutional Review Board deemed the study as low risk and exempt from formal review ((LNR/2019/QRBW/60401).
References
1. Ferraro, S, Trevisiol, C, Gion, M, Panteghini, M. Human chorionic gonadotropin assays for testicular tumors: closing the gap between clinical and laboratory practice. Clin Chem 2018;64:270–8. https://doi.org/10.1373/clinchem.2017.275263.Search in Google Scholar PubMed
2. Stenman, U, Alfthan, H, Hotakainen, K. Human chorionic gonadotropin in cancer. Clin Biochem 2004;37:549–61. https://doi.org/10.1016/j.clinbiochem.2004.05.008.Search in Google Scholar PubMed
3. Whittington, J, Fantz, CR, Gronowski, AM, McCudden, C, Mullins, R, Sokoll, L, et al.. The analytical specificity of human chorionic gonadotropin assays determined using WHO international reference reagents. Clin Chim Acta 2010;411:81–5. https://doi.org/10.1016/j.cca.2009.10.009.Search in Google Scholar PubMed
4. Pretorius, CJ, du Toit, S, Wilgen, U, Klingberg, S, Jones, M, Ungerer, JPJ, et al.. How comparable are total human chorionic gonadotropin (hCGt) tumour markers assays? Clin Chem Lab Med 2020;58:438–44. https://doi.org/10.1515/cclm-2019-0457.Search in Google Scholar PubMed
5. Lempiäinen, A, Stenman, U, Blomqvist, C, Hotakainen, K. Free β-subunit of human chorionic gonadotropin in serum is a diagnostically sensitive marker of seminomatous testicular cancer. Clin Chem 2008;54:840–3. https://doi.org/10.1373/clinchem.2008.108548.Search in Google Scholar PubMed
6. Greene, DN, Petrie, MS, Pyle, AL, Kamer, SM, Grenache, DG. Performance characteristics of the Beckman Coulter total βHCG (5th IS) assay. Clin Chim Acta 2015;439:61–7. https://doi.org/10.1016/j.cca.2014.09.029.Search in Google Scholar PubMed
7. Alfthan, H, Haglund, C, Dabek, J, Stenman, UH. Concentrations of human choriogonadotropin, its beta-subunit, and the core fragment of the beta-subunit in serum and urine of men and nonpregnant women. Clin Chem 1992;38:1981–7. https://doi.org/10.1093/clinchem/38.10.1981.Search in Google Scholar
8. Potluri, K, Moldenhauer, J, Karlman, R, Hou, S. Beta HCG levels in a pregnant dialysis patient: a cautionary tale. NDT Plus 2011;4:42–3. https://doi.org/10.1093/ndtplus/sfq195.Search in Google Scholar PubMed PubMed Central
9. Azimi, V, Budelier, VM, Gronowski, AM. Decreased renal function is associated with mild elevations of hCG in women >40 years of age. (Letter). Clin Chem 2021;11:1567–9. https://doi.org/10.1093/clinchem/hvab177.Search in Google Scholar PubMed
10. Pretorius, CJ, Parsonage, W, Cullen, LW, Wilgen, U, De Waal, E, Klingberg, S, et al.. Evaluation of the Atellica TnIH cardiac troponin I assay and assessment of biological equivalence. Clin Chem Lab Med 2022;60:283–90. https://doi.org/10.1515/cclm-2021-0991.Search in Google Scholar PubMed
11. Wehmann, RE, Amr, S, Rosa, C, Nisula, BC. Metabolism, distribution and excretion of purified human chorionic gonadotropin and its subunits in man. Ann Endocrinol (Paris) 1984;45:291–5.Search in Google Scholar
12. Valentin, M, Muller, F, Beaujard, MP, Dreux, S, Czerkiewicz, I, Meyer, V, et al.. First-trimester combined screening for trisomy 21 in women with renal disease. Prenat Diagn 2015;35:244–8. https://doi.org/10.1002/pd.4528.Search in Google Scholar PubMed
13. Skiba, R, Matyjek, A, Syryło, T, Niemczyk, S, Rymarz, A. Advanced chronic kidney disease is a strong predictor of hypogonadism and is associated with decreased lean tissue mass. Int J Nephrol Renovascular Dis 2020;13:319–27. https://doi.org/10.2147/ijnrd.s275554.Search in Google Scholar
14. Fizazi, K, Culine, S, Kramar, A, Amato, RJ, Bouzy, J, Chen, I, et al.. Early predicted time to normalization of tumor markers predicts outcome in poor-prognosis nonseminomatous germ cell tumors. J Clin Oncol 2004;22:3868–76. https://doi.org/10.1200/jco.2004.04.008.Search in Google Scholar
15. Saller, B, Clara, R, Spöttl, G, Siddle, K, Mann, K. Testicular cancer secretes intact human choriogonadotropin (hCG) and its free beta-subunit: evidence that hCG (+hCG-beta) assays are the most reliable in diagnosis and follow-up. Clin Chem 2000;36:234–9.10.1093/clinchem/36.2.234Search in Google Scholar
16. Madersbacher, S, Klieber, R, Mann, K, Marth, C, Tabarelli, M, Wick, G, et al.. Free α-subunit, free β-subunit of human chorionic gonadotropin (hCG), and intact hCG in sera of healthy individuals and testicular cancer patients. Clin Chem 1992;38:370–6. https://doi.org/10.1093/clinchem/38.3.370.Search in Google Scholar
17. Hoshi, S, Suzuki, K, Ishidoya, S, Ohyama, C, Sato, M, Namima, T, et al.. Significance of simultaneous determination of serum human chorionic gonadotropin (hCG) and hCG-beta in testicular tumor patients. Int J Urol 2000;7:218–23. https://doi.org/10.1046/j.1442-2042.2000.00181.x.Search in Google Scholar PubMed
18. Lempiäinen, A, Hotakainen, K, Blomqvist, C, Alfthan, H, Stenman, U. Increased human chorionic gonadotropin due to hypogonadism after treatment of a testicular seminoma (letter). Clin Chem 2007;53:1560–1. https://doi.org/10.1373/clinchem.2007.088518.Search in Google Scholar PubMed
19. Ferraro, S, Panteghini, M. A step forward in identifying the right human chorionic gonadotropin assay for testicular cancer. Clin Chem Lab Med 2020;58:357–60. https://doi.org/10.1515/cclm-2019-0319.Search in Google Scholar PubMed
20. Ferraro, S, Incarbone, G, Rossi, R, Dolci, A, Panteghini, M. Human chorionic gonadotropin in oncology: a matter of tight (bio)marking. Clin Chem Lab Med 2020;58:e57–60. https://doi.org/10.1515/cclm-2019-0629.Search in Google Scholar PubMed
21. Trapé, J, Franquesa, J, Sala, M, Domenech, M, Montesinos, J, Catot, S, et al.. Determination of biological variation of α-fetoprotein and choriogonadotropin (β chain) in disease-free patients with testicular cancer. Clin Chem Lab Med 2010;48:1799–801. https://doi.org/10.1515/cclm.2010.343.Search in Google Scholar
22. Ferraro, S, Panzeri, A, Braga, F, Panteghini, M. Serum α-fetoprotein in pediatric oncology: not a children’s tale. Clin Chem Lab Med 2019;57:783–97. https://doi.org/10.1515/cclm-2018-0803.Search in Google Scholar PubMed
Supplementary Material
This article contains supplementary material (https://doi.org/10.1515/cclm-2022-1240).
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