Comparison of two immunoassays for the measurement of serum HE4 for ovarian cancer

Chloe E Barr; Garth Funston; Luke T A Mounce; Phillip W Pemberton; Jonathon D Howe; Emma J Crosbie

doi:10.1016/j.plabm.2021.e00235

Comparison of two immunoassays for the measurement of serum HE4 for ovarian cancer

Pract Lab Med. 2021 May 9:26:e00235. doi: 10.1016/j.plabm.2021.e00235. eCollection 2021 Aug.

Authors

Chloe E Barr¹, Garth Funston², Luke T A Mounce³, Phillip W Pemberton⁴, Jonathon D Howe⁴, Emma J Crosbie^{1

5}

Affiliations

¹ Division of Gynaecology, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.
² The Primary Care Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
³ Institute of Health Research, University of Exeter Medical School, Exeter, UK.
⁴ Department of Clinical Biochemistry, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.
⁵ Division of Cancer Sciences, University of Manchester, Faculty of Biology, Medicine and Health, Manchester, UK.

Abstract

Introduction: The use of Human Epididymis Protein 4 (HE4) as a biomarker for ovarian cancer is gaining traction, providing the impetus for development of a high throughput automated HE4 assay that is comparable to the conventional manual enzyme immunometric-assay (EIA). The aim of this study was to compare two immunoassay methods for the measurement of serum HE4.

Materials and methods: 1348 serum samples were analysed for serum HE4 using both the EIA and the automated chemiluminescent immunoassay (CLEIA) methods. HE4 values were compared using a Passing-Bablok regression and agreement assessed using Lin's concordance correlation coefficient (CCC). The absolute and percentage bias of the CLEIA compared to EIA was determined.

Results: There was moderate agreement between the two methods (CCC 0.929, 95%CI 0.923-0.936). Passing-Bablok regression demonstrated an overestimation of the CLEIA [constant 4.44 (95%CI 2.96-5.68), slope 1.04 (95%CI 1.02-1.07)]. The CLEIA method had a mean percentage bias of 16.25% compared to the EIA method.

Conclusion: The CLEIA significantly overestimated serum HE4 values compared to the EIA, which could impact clinical interpretation and patient management. Further studies are required to develop an appropriate cut-off depending on the population being investigated and the analytic method being used.

Keywords: Biomarker; HE4; Immunoassay; Ovarian cancer detection.