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Verification of the harmonization of human epididymis protein 4 assays

  • Simona Ferraro EMAIL logo , Simona Borille , Assunta Carnevale , Erika Frusciante , Niccolò Bassani and Mauro Panteghini
Published/Copyright: March 30, 2016
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Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 54 Issue 10

Abstract

Background:

Serum human epididymis protein 4 (HE4) has gained relevance as an ovarian cancer (OC) biomarker and new automated methods have replaced the first released manual EIA by tracing results to it. We verified agreement and bias of automated methods vs. EIA as well as possible effects on patients’ management.

Methods:

One hundred and fifteen serum samples were measured by Abbott Architect i2000, Fujirebio Lumipulse G1200, Roche Modular E170, and Fujirebio EIA. Passing-Bablok regression was used to compare automated assays to EIA and agreement between methods was estimated by Lin’s concordance correlation coefficient (CCC). The bias vs. EIA was estimated and compared to specifications derived from HE4 biological variation.

Results:

Median (25th–75th percentiles) HE4 concentrations (pmol/L) were 84.5 (60.1–148.8) for EIA, 82.7 (50.3–153.9) for Abbott, 89.1 (55.2–154.9) for Roche, and 112.2 (67.8–194.2) for Fujirebio. Estimated regressions and agreements (95% confidence interval) were: Abbott=1.01(0.98–1.03) EIA–4.8(–7.5/–2.6), CCC=0.99(0.99–1.00); Roche=0.91(0.89–0.93) EIA+5.7(4.2/8.0), CCC=0.98(0.98–0.99); Fujirebio=1.20(1.17–1.24) EIA+ 2.4(–0.6/4.9), CCC=0.97(0.96–0.98). The average bias vs. EIA resulted within the desirable goal for Abbott [–3.3% (–6.1/–0.5)] and Roche [–0.2% (–3.0/2.5)]. However, while for Abbott the bias was constant and acceptable along the measurement concentration range, Roche bias increased up to –28% for HE4 values >250 pmol/L. Lumipulse showed a markedly positive bias [25.3% (21.8/28.8)].

Conclusions:

Abbott and Roche assays exhibited a good comparability in the range of HE4 values around the previously recommended 140 pmol/L cut-off. For patient monitoring, however, the assay used for determining serial HE4 must not be changed as results from different systems in lower and higher concentration ranges can markedly differ.

Keywords: assay; bias; comparison; harmonization; ovarian cancer
Corresponding author: Simona Ferraro, UOC Patologia Clinica, Ospedale ‘Luigi Sacco’, Via G.B. Grassi 74, 20157 Milan, Italy, Phone: +39 02 3904 2766, Fax: +39 02 50319835, E-mail: ; and Clinical Pathology Unit, ‘Luigi Sacco’ University Hospital, Milan, Italy

Acknowledgments

We thank Abbott Diagnostics, Fujirebio Diagnostics, and Roche Diagnostics for the generous gift of HE4 reagents to carry out the study. We also thank Fujirebio for the generous loan of the Lumipulse G1200 instrument.

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

  2. Researching funding: None declared.

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. Competing interests: The manufacturers played no role in the study design, in the collection, analysis, and interpretation of data, as well as in the writing of the report and in the decision to submit the report for publication.

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Supplemental Material:

The online version of this article (DOI: 10.1515/cclm-2015-1142) offers supplementary material, available to authorized users.

Received: 2015-11-19
Accepted: 2016-2-26
Published Online: 2016-3-30
Published in Print: 2016-10-1

©2016 Walter de Gruyter GmbH, Berlin/Boston

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https://doi.org/10.1515/cclm-2015-1142
Keywords for this article
assay; bias; comparison; harmonization; ovarian cancer

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. Serum myoglobin immunoassays: obsolete or still clinically useful?
  4. Reviews
  5. Kounis syndrome: an update on epidemiology, pathogenesis, diagnosis and therapeutic management
  6. What do we know about homocysteine and exercise? A review from the literature
  7. Mini Review
  8. Osteocalcin as a potential risk biomarker for cardiovascular and metabolic diseases
  9. Opinion Paper
  10. Statistical approach for optimization of external quality assurance (EQA) studies of molecular and serological viral diagnostics
  11. EFLM Article
  12. Sample collections from healthy volunteers for biological variation estimates’ update: a new project undertaken by the Working Group on Biological Variation established by the European Federation of Clinical Chemistry and Laboratory Medicine
  13. General Clinical Chemistry and Laboratory Medicine
  14. Analyte stability during the total testing process: studies of vitamins A, D and E by LC-MS/MS
  15. Improvement in the predictive ability of the Intermountain Mortality Risk Score by adding routinely collected laboratory tests such as albumin, bilirubin, and white cell differential count
  16. Cystatin C provides a better estimate of the effect of glomerular filtration rate on serum human epididymis protein 4 concentrations
  17. Verification of the harmonization of human epididymis protein 4 assays
  18. Clinical utility of urinary liver-type fatty acid binding protein measured by latex-enhanced turbidimetric immunoassay in chronic kidney disease
  19. Comparison of three analytical platforms for quantification of the neurofilament light chain in blood samples: ELISA, electrochemiluminescence immunoassay and Simoa
  20. Reference Values and Biological Variations
  21. Distribution of antiphospholipid antibodies in a large population-based German cohort
  22. Cardiovascular Diseases
  23. Serum protein S100 as marker of postoperative delirium after off-pump coronary artery bypass surgery: secondary analysis of two prospective randomized controlled trials
  24. Infectious Diseases
  25. Copeptin predicts 10-year all-cause mortality in community patients: a 10-year prospective cohort study
  26. Clinical and laboratory findings in the diagnosis of right lower quadrant abdominal pain: outcome analysis of the APPAC trial
  27. Letters to the Editor
  28. Why a new algorithm using high-sensitivity cardiac troponins for the rapid rule-out of NSTEMI is not adapted to routine practice
  29. Optimal collection tubes for plasma glucose determination: confusion reigns supreme
  30. Long-term stability of serum samples positive for carbohydrate deficient transferrin (CDT) routinely stored at −20 °C
  31. Seasonal variations in plasma free metanephrine concentrations are not evident in the West of Ireland
  32. Potential errors in the determination of urinary ammonium by formol titration
  33. Interference by biological anti-cancer drugs in electrophoretic and immunofixation techniques
  34. A point mutation in the thiopurine S-methyltransferase gene that led to exon 5 deletion in the transcribed mRNA
  35. Detection of the heterozygote of hemoglobin Constant Spring by α-thalassemia immunochromatographic strip test
  36. Automated CH50 liposome-based immunoassay: consideration in dilution and validation of reference interval
  37. Theranos phenomenon – Part 5: Theranos’ presentation at the American Association for Clinical Chemistry Annual Conference 2016
  38. Congress Abstracts
  39. 58th National Congress of the Hungarian Society of Laboratory Medicine
  40. The 4th Joint EFLM-UEMS Congress “Laboratory Medicine at the Clinical Interface” Warsaw, Poland, 21th–24th September, 2016
  41. Congress of Clinical Chemistry and Laboratory Medicine
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