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Biological variation of CA 15-3, CA 125 and HE 4 on lithium heparinate plasma in apparently healthy Caucasian volunteers

  • Louise Guillaume ORCID logo , Virginie Chapelle , Matthieu Deltombe ORCID logo , Arnaud Nevraumont , Antoine Mairesse , Diane Maisin and Damien Gruson EMAIL logo
Published/Copyright: April 12, 2023
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Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 61 Issue 7

Abstract

Objectives

Tumor markers are well-known for being important tools in the support of diagnosis, monitoring of treatment efficacy and follow-up of cancers. CA 125, CA 15-3 and HE 4 have demonstrated potential efficacy in other clinical indications. The main objective was to evaluate the biological variation of these glycoproteins using two different immunoassays in an apparently healthy Caucasian population.

Methods

Nineteen healthy volunteers including 11 women and 8 men were sampled weekly for 5 consecutive weeks. Samples were analyzed in duplicate on Lumipulse® G600II (Fujirebio) and on the Cobas e602 (Roche Diagnostics) analyzers. After assessment of normality, exclusion of outliers and analysis of homogeneity of variance, analytical variation (CVA), within-subject biological variation (CVI) and between-subject biological variation (CVG) were determined using a nested ANOVA.

Results

CVA, CVI and CVG were determined on both analyzers and both genders. For CA 125, the CVA ranges from 1.0 to 3.4%, the CVI from 5.7 to 13.8% and the CVG from 32.2 to 42.9%. For CA 15-3, the CVA is between 1.1 and 3.4%, the CVI between 3.9 and 6.5% and the CVG between 43.7 and 196.9%. Lastly, HE 4 has CVA values between 1.4 and 2.4%, CVI between 5.1 and 10.5% and CVG between 7.1 and 12.6%.

Conclusions

Our study provided updated data on the biological variation of CA 125, HE 4 and CA 15-3. These data allow to improve the clinical interpretation and thus the management of the patient.

Keywords: biological variation; CA 125; CA 15-3; HE 4; reference change values and analytical performance specification
Corresponding author: Prof. Damien Gruson, Department of Clinical Biochemistry, Cliniques Universitaires St-Luc, Université Catholique de Louvain 10 Avenue Hippocrate, 1200, Brussels, Belgium; and Pôle de recherche en Endocrinologie, Diabète et Nutrition, Institut de Recherche Expérimentale et Clinique, Cliniques Universitaires St-Luc, Université Catholique de Louvain, Brussels, Belgium, Phone: +32-(0)2-7646747, Fax: +32-(0)2-7646930, E-mail:
Louise Guillaume, Virginie Chapelle and Matthieu Deltombe contributed equally to this work.

  1. Research funding: None declared.

  2. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  3. Competing interests: Authors state no conflict of interest.

  4. Informed consent: Informed consent was obtained from all individuals included in this study.

  5. Ethical approval: The study protocol was approved by the ethics committee of our institution (Cliniques Universitaires Saint-Luc, Brussels, Belgium; 2019/04SEP/388).

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Received: 2022-09-27
Accepted: 2023-03-17
Published Online: 2023-04-12
Published in Print: 2023-06-27

© 2023 Walter de Gruyter GmbH, Berlin/Boston

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https://doi.org/10.1515/cclm-2022-0966
Keywords for this article
biological variation; CA 125; CA 15-3; HE 4; reference change values and analytical performance specification

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. ChatGPT: Angel or Demond? Critical thinking is still needed
  4. Mini Review
  5. Diagnostic accuracy of Siemens SARS-CoV-2 Antigen (CoV2Ag) chemiluminescent immunoassay for diagnosing acute SARS-CoV-2 infection: a pooled analysis
  6. Opinion Papers
  7. Neurofilament light chain as neuronal injury marker – what is needed to facilitate implementation in clinical laboratory practice?
  8. Clinical evidence requirements according to the IVDR 2017/746: practical tools and references for underpinning clinical evidence of IVD-MDs
  9. EFLM Papers
  10. Potentials and pitfalls of ChatGPT and natural-language artificial intelligence models for the understanding of laboratory medicine test results. An assessment by the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) Working Group on Artificial Intelligence (WG-AI)
  11. Detection of antinuclear antibodies: recommendations from EFLM, EASI and ICAP
  12. Analytical aspects of the antinuclear antibody test by HEp-2 indirect immunofluorescence: EFLM report on an international survey
  13. Guidelines and Recommendations
  14. Variability of cardiac troponin levels in normal subjects and in patients with cardiovascular diseases: analytical considerations and clinical relevance
  15. General Clinical Chemistry and Laboratory Medicine
  16. Pre-analytical long-term stability of neopterin and neurofilament light in stored cerebrospinal fluid samples
  17. Development of a candidate reference measurement procedure by ID-LC-MS/MS for total tau protein measurement in cerebrospinal fluid (CSF)
  18. Assessing the commutability of candidate reference materials for the harmonization of neurofilament light measurements in blood
  19. Surface plasmon resonance assays for the therapeutic drug monitoring of infliximab indicate clinical relevance of anti-infliximab antibody binding properties
  20. An antibody-free LC-MS/MS method for the quantification of sex hormone binding globulin in human serum and plasma
  21. Accurate stratification between VEXAS syndrome and differential diagnoses by deep learning analysis of peripheral blood smears
  22. Establishing quality indicators for point of care glucose testing: recommendations from the Canadian Society for Clinical Chemists Point of Care Testing and Quality Indicators Special Interest Groups
  23. Clinical implication by differential analytical performances of serum free light chain quantitation analysis using fully automated analyzers
  24. Simultaneous analysis of antihyperglycemic small molecule drugs and peptide drugs by means of dual liquid chromatography high-resolution mass spectrometry
  25. Reference Values and Biological Variations
  26. Reference intervals for thyroid biomarkers to enhance the assessment of thyroid status in childhood and adolescence
  27. Biological variation of CA 15-3, CA 125 and HE 4 on lithium heparinate plasma in apparently healthy Caucasian volunteers
  28. Cancer Diagnostics
  29. Individual risk prediction of high grade prostate cancer based on the combination between total prostate-specific antigen (PSA) and free to total PSA ratio
  30. Cardiovascular Diseases
  31. Using logistic regression models to investigate the effects of high-sensitivity cardiac troponin T confounders on ruling in acute myocardial infarction
  32. Infectious Diseases
  33. Assessment of humoral and cellular immunity after bivalent BNT162b2 vaccination and potential association with reactogenicity
  34. Three rounds of a national external quality assessment reveal a link between disharmonic anti-SARS-CoV-2 antibody quantifications and the infection stage
  35. Corrigendum
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  37. Letters to the Editor
  38. Please do not call it Theranos
  39. Lot-to-lot bias for high-sensitivity cardiac troponin I concentrations ≥1000 ng/L
  40. Lot-to-lot reagent changes and commutability of quality testing materials for total bile acid measurements
  41. On the importance of sampling interval in studies of biological variation in thyroid function
  42. Stability of plasma renin concentration based on plasma freezing time, as an adjunct to the stability data reported in the paper by Hepburn and others
  43. Falsely low beta-hCG results in pregnant woman on Siemens Atellica: don’t forget the “hook effect”
  44. Proenkephalin A 119–159 (penKid) – a novel biomarker and its quantification on the Nexus IB10 POC system for assessing kidney function
  45. Investigating the polyuria-polydipsia syndrome: the “PP” Shiny app
  46. Evaluation of a novel, stand-alone system to measure interleukin-6
  47. Spurious low WBC count in the WNR channel of Sysmex XN-9000 hematology analyzer in a case with leukocyte aggregation
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