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pISSN 2950-9114 eISSN 2950-9122
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Original Article

J Lab Med Qual Assur 2014; 36(3): 149-156

Published online September 30, 2014


Copyright © Korean Association of External Quality Assessment Service.

Performance Evaluation of the ARCHITECT HE4 Assay

Eun-Jung Cho, Dae- Hyun Ko, Tae-Dong Jeong, Woochang Lee, Sail Chun, and Won-Ki Min

Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

Correspondence to:Woochang Lee
Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 138-736, Korea
Tel: +82-2-3010-4506
Fax: +82-2-478-0884
E-mail: wlee1@amc.seoul.kr

Received: August 15, 2014; Revised: September 2, 2014; Accepted: September 10, 2014

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Background: Human epididymis protein 4 (HE4) is known to be overexpressed in ovarian cancer, and therefore, it can be considered an important biomarker of epithelial ovarian cancer. HE4 shows higher specificity than cancer antigen 125 (CA-125); this characteristic can be used to discriminate between benign and malignant pelvic masses. The Risk of Ovarian Malignancy Algorithm (ROMA) value based on the results obtained for CA-125 and HE4 is used for risk assessment for ovarian cancer. The aim of this study is to evaluate the performance of ARCHITECT HE4 assay (Abbott Laboratories, US) and ROMA value. Methods: Precision, linearity, limit of blank (LoB), and limit of detection (LoD) values were evaluated on the basis of the guidelines supplied by the Clinical and Laboratory Standards Institute. All assay procedures were performed on an Architect i2000 analyzer (Abbott Laboratories, US) using the ARCHITECT HE4 assay reagent. ARCHITECT HE4 quality control materials, calibrator B, calibrator F, multi assay diluent, and patient serum samples were used for the assay. ROMA values (%) were calculated for patients and healthy controls based on their menopausal state. Results: A total CV of 3% was noted for precision analysis. Linearity was confirmed in the analytic measurement range (AMR). LoB and LoD values were below the lower limit of AMR. The ROMA values for patients with ovarian cancer were higher than those for healthy controls. Conclusions: The ARCHITECT HE4 assay showed suitable analytical performance characteristics with respect to precision, linearity, LoB, and LoD. This assay, along with ROMA values, is expected to be widely used for rapid risk assessment and differential diagnosis of patients with pelvic mass. (J Lab Med Qual Assur 2014;36:149-156)

Keywords: HE4, Ovarian neoplasms, Risk

  1. Jung KW, Won YJ, Kong HJ, Oh CM, Lee DH, Lee JS. Prediction of cancer incidence and mortality in Korea, 2014. Cancer Res Treat 2014;46:124-30.
    Pubmed KoreaMed CrossRef
  2. Andersen MR, Goff BA, Lowe KA, Scholler N, Bergan L, Dresher CW, et al. Combining a symptoms index with CA 125 to improve detection of ovarian cancer. Cancer 2008;113:484-9.
    Pubmed KoreaMed CrossRef
  3. Ortiz-Munoz B, Aznar-Oroval E, Garcia Garcia A, Covisa Peris A, Perez Ballestero P, Sanchez Yepes M, et al. HE4, Ca125 and ROMA algorithm for differential diagnosis between benign gynaecological diseases and ovarian cancer. Tumour Biol 2014;35:7249-58.
    Pubmed CrossRef
  4. Sandri MT, Bottari F, Franchi D, Boveri S, Candiani M, Ronzoni S, et al. Comparison of HE4, CA125 and ROMA algorithm in women with a pelvic mass: correlation with pathological outcome. Gynecol Oncol 2013;128:233-8.
    Pubmed CrossRef
  5. Li F, Tie R, Chang K, Wang F, Deng S, Lu W, et al. Does risk for ovarian malignancy algorithm excel human epididymis protein 4 and CA125 in predicting epithelial ovarian cancer: a meta-analysis. BMC Cancer 2012;12:258.
    Pubmed KoreaMed CrossRef
  6. Fuith LC. The distribution of CA125 in the reproductive tract of pregnant and non-pregnant women. Br J Obstet Gynaecol 1989;96:750.
    Pubmed CrossRef
  7. Holcomb K, Vucetic Z, Miller MC, Knapp RC. Human epididymis protein 4 offers superior specificity in the differentiation of benign and malignant adnexal masses in premenopausal women. Am J Obstet Gynecol 2011;205:358.e1-6.
    Pubmed CrossRef
  8. Drapkin R, von Horsten HH, Lin Y, Mok SC, Crum CP, Welch WR, et al. Human epididymis protein 4 (HE4) is a secreted glycoprotein that is overexpressed by serous and endometrioid ovarian carcinomas. Cancer Res 2005;65:2162-9.
    Pubmed CrossRef
  9. Moore RG, Brown AK, Miller MC, Skates S, Allard WJ, Verch T, et al. The use of multiple novel tumor biomarkers for the detection of ovarian carcinoma in patients with a pelvic mass. Gynecol Oncol 2008;108:402-8.
    Pubmed CrossRef
  10. Van Gorp T, Veldman J, Van Calster B, Cadron I, Leunen K, Amant F, et al. Subjective assessment by ultrasound is superior to the risk of malignancy index (RMI) or the risk of ovarian malignancy algorithm (ROMA) in discriminating benign from malignant adnexal masses. Eur J Cancer 2012;48:1649-56.
    Pubmed CrossRef
  11. Escudero JM, Auge JM, Filella X, Torne A, Pahisa J, Molina R. Comparison of serum human epididymis protein 4 with cancer antigen 125 as a tumor marker in patients with malignant and nonmalignant diseases. Clin Chem 2011;57:1534-44.
    Pubmed CrossRef
  12. Clinical and Laboratory Standards Institute. Evaluation of precision performance of quantitative measurement methods: approved guideline. CLSI document EP5-A2. 2nd ed. Wayne (PA): Clinical and Laboratory Standards Institute, 2004.
  13. Clinical and Laboratory Standards Institute. Evaluation of the linearity of quantitative measurement procedures: a statistical approach: approved guideline. CLSI document EP6-A. Wayne (PA): Clinical and Laboratory Standards Institute, 2003.
  14. Clinical and Laboratory Standards Institute. Evaluation of detection capability for clinical laboratory measurement procedures: approved guideline. CLSI document EP17A2. 2nd ed. Wayne (PA): Clinical and Laboratory Standards Institute, 2012.
  15. Simmons AR, Baggerly K, Bast RC Jr. The emerging role of HE4 in the evaluation of epithelial ovarian and endometrial carcinomas. Oncology (Williston Park) 2013;27:548-56.
  16. Bast RC Jr, Badgwell D, Lu Z, Marquez R, Rosen D, Liu J, et al. New tumor markers: CA125 and beyond. Int J Gynecol Cancer 2005;15 Suppl 3:274-81.
    Pubmed CrossRef
  17. Hellstrom I, Raycraft J, Hayden-Ledbetter M, Ledbetter JA, Schummer M, McIntosh M, et al. The HE4 (WFDC2) protein is a biomarker for ovarian carcinoma. Cancer Res 2003;63:3695-700.
  18. Moore RG, Miller MC, Steinhoff MM, Skates SJ, Lu KH, Lambert-Messerlian G, et al. Serum HE4 levels are less frequently elevated than CA125 in women with benign gynecologic disorders. Am J Obstet Gynecol 2012;206:351.e1-8.
    Pubmed KoreaMed CrossRef
  19. Farzaneh F, Honarvar Z, Yaraghi M, Yaseri M, Arab M, Hosseini M, et al. Preoperative evaluation of risk of ovarian malignancy algorithm index in prediction of malignancy of adnexal masses. Iran Red Crescent Med J 2014;16:e17185.
    Pubmed KoreaMed CrossRef
  20. Kadija S, Stefanovic A, Jeremic K, Radojevic MM, Nikolic L, Markovic I, et al. The utility of human epididymal protein 4, cancer antigen 125, and risk for malignancy algorithm in ovarian cancer and endometriosis. Int J Gynecol Cancer 2012;22:238-44.
    Pubmed CrossRef
  21. Sturgeon CM, Hoffman BR, Chan DW, Ch’ng SL, Hammond E, Hayes DF, et al. National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines for use of tumor markers in clinical practice: quality requirements. Clin Chem 2008;54:e1-e10.
  22. Fraser CG, Hyltoft Petersen P, Libeer JC, Ricos C. Proposals for setting generally applicable quality goals solely based on biology. Ann Clin Biochem 1997;34 ( Pt 1):8-12.
    Pubmed CrossRef
  23. Hallamaa M, Huhtinen K, Suvitie P, Perheentupa A. Serum concentrations of HE4 change little during in vitro fertilization. Acta Obstet Gynecol Scand 2014;93:640-6.
    Pubmed CrossRef
  24. Kong SY, Han MH, Yoo HJ, Hwang JH, Lim MC, Seo SS, et al. Serum HE4 level is an independent prognostic factor in epithelial ovarian cancer. Ann Surg Oncol 2012;19:1707-12.
    Pubmed CrossRef
  25. US Department of Health and Human Services. Draft guidance for industry, clinical laboratories, and staff: in vitro diagnostic multivariate index assays. http://www.fda.gov/downloads/medicaldevices/deviceregulationandguidance/guidancedocuments/ucm071455.pdf(Accessed Sep 4, 2014).
  26. Moore RG, Miller MC, Disilvestro P, Landrum LM, Gajewski W, Ball JJ, et al. Evaluation of the diagnostic accuracy of the risk of ovarian malignancy algorithm in women with a pelvic mass. Obstet Gynecol 2011;118(2 Pt 1):280-8.
    Pubmed KoreaMed CrossRef
  27. Jacob F, Meier M, Caduff R, Goldstein D, Pochechueva T, Hacker N, et al. No benefit from combining HE4 and CA125 as ovarian tumor markers in a clinical setting. Gynecol Oncol 2011;121:487-91.
    Pubmed CrossRef

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