A step forward in identifying the right human chorionic gonadotropin assay for testicular cancer
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Simona Ferraro
und
Mauro Panteghini
Abstract
Clinical practice guidelines for the management of germ cell tumors recommend the measurements of human chorionic gonadotropin (hCG) and/or free hCGβ subunit for earlier diagnosis/recognition of the residual disease, for the prognostic evaluation and for the post-chemotherapy surveillance. However, the marketed hCG assays are validated and approved only for pregnancy purposes, with the sole exception of the Elecsys ‘hCG+β’ assay (Roche Diagnostics), cleared in Europe for oncological application. Theoretically, the hCG assay design for oncological purposes should fulfil the recommendations of the International Society of Oncology and Biomarkers requiring the use of antibodies displaying an equimolar recognition of both intact hCG and hCGβ monomer. Further analytical requirements should also be considered, such as optimal analytical sensitivity to allow an early tumor detection and low cross-reactivity for luteinizing hormone (LH). For the Elecsys assay, the detection limit (0.2 U/L) and the reported cross-reactivity for LH (0.12%) may be considered adequate if compared with the recommended requirements. Another issue is the definition of decision limits for oncologic purposes. After 3 years of clinical experience using the Elecsys assay in the oncology setting, we were able to define limits partitioned by sex and age as follows: males <50 years, 0.3 U/L; males >50 years, 2.3 U/L; female <50 years, 2.1 U/L; female >50 years, 5.6 U/L. There is an urgent need to disseminate appropriate educational information and to boost the clinical use of selective, highly sensitive and precise assays, specifically manufactured for cancer application.
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: None declared.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
References
1. Horwich A, Shipley J, Huddart R. Testicular germ-cell cancer. Lancet 2006;367:754–65.10.1016/S0140-6736(06)68305-0Suche in Google Scholar
2. Gilligan TD, Seidenfeld J, Basch EM, Einhorn LH, Fancher T, Smith DC, et al. American Society of Clinical Oncology Clinical Practice Guideline on uses of serum tumor markers in adult males with germ cell tumors. J Clin Oncol 2010;28:3388–404.10.1200/JCO.2009.26.4481Suche in Google Scholar
3. 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;64:270–8.10.1373/clinchem.2017.275263Suche in Google Scholar
4. Berger P, Paus E, Hemken PM, Sturgeon C, Stewart WW, Skinner JP, et al. Candidate epitopes for measurement of hCG and related molecules: the second ISOBM TD-7 workshop. Tumour Biol 2013;34:4033–57.10.1007/s13277-013-0994-6Suche in Google Scholar
5. Sturgeon CM, Duffy MJ, Stenman UH, Lilja H, Brünner N, Chan DW, et al. National Academy of Clinical Biochemistry laboratory medicine practice guidelines for use of tumor markers in testicular, prostate, colorectal, breast, and ovarian cancers. Clin Chem 2008;54:e11–79.10.1373/clinchem.2008.105601Suche in Google Scholar
6. Anckaert E, Ver Elst K, Mees M, Lecomte S, De Bock S, Schiettecatte J. Analytical and clinical evaluation of a human chorionic gonadotrophin plus β (hCG+βhCG) immunoassay in germ cell tumours and gestational trophoblastic disease. Immuno-Anal Biol Spe 2005;20:11–5.10.1016/j.immbio.2004.12.003Suche in Google Scholar
7. Lempiäinen A, Hotakainen K, Blomqvist C, Alfthan H, Stenman UH. Increased human chorionic gonadotropin due to hypogonadism after treatment of a testicular seminoma. Clin Chem 2007;53:1560–1.10.1373/clinchem.2007.088518Suche in Google Scholar
8. Sölétormos G, Schiøler V, Nielsen D, Skovsgaard T, Dombernowsky P. Interpretation of results for tumor markers on the basis of analytical imprecision and biological variation. Clin Chem 1993;39:2077–83.10.1093/clinchem/39.10.2077Suche in Google Scholar
9. Lange PH, Vogelzang NJ, Goldman A, Kennedy BJ, Fraley EE. Marker half-life analysis as a prognostic tool in testicular cancer. J Urol 1982;128:708–11.10.1016/S0022-5347(17)53149-3Suche in Google Scholar
10. Fizazi K, Pagliaro L, Laplanche A, Fléchon A, Mardiak J, Geoffrois L. Personalised chemotherapy based on tumour marker decline in poor prognosis germ-cell tumours (GETUG 13): a phase 3, multicentre, randomised trial. Lancet Oncol 2014;15:1442–50.10.1016/S1470-2045(14)70490-5Suche in Google Scholar
11. Wymer KM, Pearce SM, Harris KT, Pierorazio PM, Daneshmand S, Eggener SE. Adherence to National Comprehensive Cancer Network® Guidelines for Testicular Cancer. J Urol 2017;197:684–9.10.1016/j.juro.2016.09.073Suche in Google Scholar PubMed
12. Cathomas R, Klingbiel D, Bernard BD, Lorch A, del Muro XG, Morelli F, et al. FDG PET scan (PET) positive residual lesions after chemotherapy (chemo) for metastatic seminoma: results of an International Global Germ Cell Cancer Group (G3) registry. J Clin Oncol 2017;35(Suppl):abstract 4521.10.1200/JCO.2017.35.15_suppl.4521Suche in Google Scholar
13. 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;22:3868–76.10.1200/JCO.2004.04.008Suche in Google Scholar PubMed
14. 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;38:1981–7.10.1093/clinchem/38.10.1981Suche in Google Scholar
15. Cole LA, Gutierrez JM. Production of human chorionic gonadotropin during the normal menstrual cycle. J Reprod Med 2009;54:245–50.Suche in Google Scholar
©2020 Walter de Gruyter GmbH, Berlin/Boston
Artikel in diesem Heft
- Frontmatter
- Editorial
- Progress in understanding the use of human chorionic gonadotropin as a tumor marker
- Reviews
- Biomarkers for prostate cancer: prostate-specific antigen and beyond
- Gut microbiome investigation in celiac disease: from methods to its pathogenetic role
- Opinion Papers
- Understanding and managing interferences in clinical laboratory assays: the role of laboratory professionals
- A step forward in identifying the right human chorionic gonadotropin assay for testicular cancer
- EFLM Opinion Paper
- Validation and verification of examination procedures in medical laboratories: opinion of the EFLM Working Group Accreditation and ISO/CEN standards (WG-A/ISO) on dealing with ISO 15189:2012 demands for method verification and validation
- Guidelines and Recommendations
- An updated protocol based on CLSI document C37 for preparation of off-the-clot serum from individual units for use alone or to prepare commutable pooled serum reference materials
- General Clinical Chemistry and Laboratory Medicine
- Highly accurate and explainable detection of specimen mix-up using a machine learning model
- Impact of delta check time intervals on error detection capability
- Effect of long-term frozen storage and thawing of stool samples on faecal haemoglobin concentration and diagnostic performance of faecal immunochemical tests
- A more accurate prediction to rule in and rule out pre-eclampsia using the sFlt-1/PlGF ratio and NT-proBNP as biomarkers
- Macro vitamin B12: an underestimated threat
- Evaluation of the primary biliary cholangitis-related serologic profile in a large cohort of Belgian systemic sclerosis patients
- High frequency of anti-parietal cell antibody (APCA) and intrinsic factor blocking antibody (IFBA) in individuals with severe vitamin B12 deficiency – an observational study in primary care patients
- DOAC-Remove abolishes the effect of direct oral anticoagulants on activated protein C resistance testing in real-life venous thromboembolism patients
- Cancer Diagnostics
- How comparable are total human chorionic gonadotropin (hCGt) tumour markers assays?
- Diabetes
- Measurement accuracy of two professional-use systems for point-of-care testing of blood glucose
- Letters to the Editor
- Human chorionic gonadotropin in oncology: a matter of tight (bio)marking
- More robust analytical evidence should support the selection of human chorionic gonadotropin assays for oncology application
- Letter in reply to the letter to the editor of Ferraro S and Panteghini M with the title “More robust analytical evidence should support the selection for human chorionic gonadotropin assays for oncology application”
- Definition of analytical quality specifications for serum total folate measurements using a simulation outcome-based model
- Alarmed by misleading interference in free T3 and free T4 assays: a new case of anti-streptavidin antibodies
- A root cause analysis of ‘falsely elevated’ oxygen saturation: investigation of pneumatic tube transport and differences between estimated and measured saturation in a critical patient population
- The chaos of serologic markers in interstitial pneumonia with autoimmune features can be corrected by the laboratory physician
- Vitamin A and E gender and age stratification in adults
- Detection of monoclonal B-lymphocytosis: interest of cellular population data and CytoDiff™ analysis
- Urinary reference intervals for gadolinium in individuals without recent exposure to gadolinium-based contrast agents
- Molecular diagnosis of toxoplasmosis: evaluation of automated DNA extraction using eMAG® (bioMérieux) on buffy coat, cerebrospinal and bronchoalveolar lavage fluids
- Retraction
- Retraction of: The Effect of a Gender Difference in the Apolipoprotein E Gene DNA Polymorphism on Serum Lipid Levels in a Serbian Healthy Population
Artikel in diesem Heft
- Frontmatter
- Editorial
- Progress in understanding the use of human chorionic gonadotropin as a tumor marker
- Reviews
- Biomarkers for prostate cancer: prostate-specific antigen and beyond
- Gut microbiome investigation in celiac disease: from methods to its pathogenetic role
- Opinion Papers
- Understanding and managing interferences in clinical laboratory assays: the role of laboratory professionals
- A step forward in identifying the right human chorionic gonadotropin assay for testicular cancer
- EFLM Opinion Paper
- Validation and verification of examination procedures in medical laboratories: opinion of the EFLM Working Group Accreditation and ISO/CEN standards (WG-A/ISO) on dealing with ISO 15189:2012 demands for method verification and validation
- Guidelines and Recommendations
- An updated protocol based on CLSI document C37 for preparation of off-the-clot serum from individual units for use alone or to prepare commutable pooled serum reference materials
- General Clinical Chemistry and Laboratory Medicine
- Highly accurate and explainable detection of specimen mix-up using a machine learning model
- Impact of delta check time intervals on error detection capability
- Effect of long-term frozen storage and thawing of stool samples on faecal haemoglobin concentration and diagnostic performance of faecal immunochemical tests
- A more accurate prediction to rule in and rule out pre-eclampsia using the sFlt-1/PlGF ratio and NT-proBNP as biomarkers
- Macro vitamin B12: an underestimated threat
- Evaluation of the primary biliary cholangitis-related serologic profile in a large cohort of Belgian systemic sclerosis patients
- High frequency of anti-parietal cell antibody (APCA) and intrinsic factor blocking antibody (IFBA) in individuals with severe vitamin B12 deficiency – an observational study in primary care patients
- DOAC-Remove abolishes the effect of direct oral anticoagulants on activated protein C resistance testing in real-life venous thromboembolism patients
- Cancer Diagnostics
- How comparable are total human chorionic gonadotropin (hCGt) tumour markers assays?
- Diabetes
- Measurement accuracy of two professional-use systems for point-of-care testing of blood glucose
- Letters to the Editor
- Human chorionic gonadotropin in oncology: a matter of tight (bio)marking
- More robust analytical evidence should support the selection of human chorionic gonadotropin assays for oncology application
- Letter in reply to the letter to the editor of Ferraro S and Panteghini M with the title “More robust analytical evidence should support the selection for human chorionic gonadotropin assays for oncology application”
- Definition of analytical quality specifications for serum total folate measurements using a simulation outcome-based model
- Alarmed by misleading interference in free T3 and free T4 assays: a new case of anti-streptavidin antibodies
- A root cause analysis of ‘falsely elevated’ oxygen saturation: investigation of pneumatic tube transport and differences between estimated and measured saturation in a critical patient population
- The chaos of serologic markers in interstitial pneumonia with autoimmune features can be corrected by the laboratory physician
- Vitamin A and E gender and age stratification in adults
- Detection of monoclonal B-lymphocytosis: interest of cellular population data and CytoDiff™ analysis
- Urinary reference intervals for gadolinium in individuals without recent exposure to gadolinium-based contrast agents
- Molecular diagnosis of toxoplasmosis: evaluation of automated DNA extraction using eMAG® (bioMérieux) on buffy coat, cerebrospinal and bronchoalveolar lavage fluids
- Retraction
- Retraction of: The Effect of a Gender Difference in the Apolipoprotein E Gene DNA Polymorphism on Serum Lipid Levels in a Serbian Healthy Population
