Assessment of diagnostic value of ‘Human Epididymis Factor 4 (HE4)’ in women with adnexal masses

Derya Kılıç; Hakan Yetimalar; Gülcan Sağlam; Mehmet Köseoğlu

doi:10.31362/patd.712419

Research Article

BibTex

RIS

Cite

Assessment of diagnostic value of ‘Human Epididymis Factor 4 (HE4)’ in women with adnexal masses

Year 2020, Volume: 13 Issue: 2, 403 - 413, 14.05.2020

Derya Kılıç Hakan Yetimalar Gülcan Sağlam Mehmet Köseoğlu

https://doi.org/10.31362/patd.712419

Abstract

Purpose: Human epididymis protein 4 (HE4) is a novel biomarker for ovarian cancers. The aim of this study is to assess the usefulness and efficacy of HE4, in comparison with CA-125 in the differential diagnosis of malignant and benign gynecological diseases in women with adnexal masses.
Materials and Methods: 85 patients diagnosed with adnexial mass who were operated at a tertiary referral center between the years of 2012 and 2013 were included in the study. Demographic data, physical examination, results of the laboratory tests, imaging, and pathology were recorded from all subjects. Blood samples were collected before surgery for the evaluation of HE4 and CA-125 levels. Patients were divided into 4 groups according to their histopathologic diagnosis: benign (n:58), malignant (n:17), borderline (n:5) and metastatic (n:5) and serum CA-125 and HE4 levels were compared considering menopausal status.
Results: Using 35 U/mL as the cut-off value, CA-125 had a sensitivity of 82.4%, spesificity of 67.2%, a negative predictive value of 92.9%, and a positive predictive value of %42.4%. For the same sensitivity level, specificity was 87.9%, negative predictive value was 94.4%, and the positive predictive value was 66.7% for HE4. Receiver operator characteristic (ROC) area under the curve was higher in both the premenopausal and postmenopausal group for the HE4 curve. Accordingly, sensitivity at set specificity of 90% was 82.4%, and 70.6% for 95% of specificity and 41.1% for 98%. Same sensitivity values for CA-125 were 47.1%, 35.3% and 23.5%, respectively.
Conclusion: According to our study, especially in the premenopausal period, HE4 shows higher sensitivity and specificity values than CA-125.

Keywords

adnexal mass, ovarian cancer, CA-125, HE4

References

1) NIH consensus conference. Ovarian cancer. Screening, treatment, and follow up. NIH Consensus Development Panel on Ovarian Cancer. JAMA 1995;273:491-497.
2) Henderson JT, Webber EM, Sawaya GF. Screening for Ovarian Cancer: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force. JAMA. 2018;319:595-606. doi: 10.1001/jama.2017.21421. Review. PubMed PMID: 29450530.
3) Walker M, Sobel M. Diagnosing ovarian cancer. CMAJ. 2018;190:E1259. doi: 10.1503/cmaj.180499. PubMed PMID: 30348741; PubMed Central PMCID: PMC6199160.
4) Yang WL, Lu Z, Bast RC Jr. The role of biomarkers in the management of epithelial ovarian cancer. Expert Rev Mol Diagn. 2017;17:577-591. doi: 10.1080/14737159.2017.1326820. Epub 2017 May 15. Review. PubMed PMID: 28468520; PubMed Central PMCID: PMC5823503.
5) 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;15:274–281.
6) Buys SS, Partridge E, Greene MH, Prorok PC, Reding D, Riley TL, et al. Ovarian cancer screening in the Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening trial: findings from the initial screen of a randomized trial. Am J Obstet Gynecol 2005;193:1630–1639.
7) Fritsche HA, Bast RC. CA 125 in ovarian cancer: advances and controversy. Clin Chem 1998;44:1379–1380.
9) Moore RG, Brown AK, Miller MC, et al. The use of multiple novel tumor biomarkers for the detection of ovarian carcinoma in patients with a pelvic mass. Gynecol Oncol 2008;108:402–408.
10)Yesilyurt H, Seckin B, Aktulay A, Ozyer S. Age-stratified analysis of tumor markers and tumor characteristics in adolescents and young women with mature cystic teratoma. J Chin Med Assoc. 2018;81:499-504. doi: 10.1016/j.jcma.2017.07.005. Epub 2017 Aug 18. PubMed PMID: 28826726.
11) Hindman N, VanBuren W. Imaging Spectrum of Endometriosis (Endometriomas to Deep Infiltrative Endometriosis). Radiol Clin North Am. 2020;58:275-289. doi: 10.1016/j.rcl.2019.11.001. Review. PubMed PMID: 32044007.
12) Huhtinen K, Suvitie P, Hiissa J, Junnila J, Huvila J, Kujari H, et al. Serum HE4 concentration differentiates malignant ovarian tumours from ovarian endometriotic cysts. Br J Cancer 2009;100:1315–1319.
13) Lowe KA, Shah C, Wallace E, et al. Effects of personal characteristics on serum CA125, mesothelin, and HE4 levels in healthy postmenopausal women at high-risk for ovarian cancer. Cancer Epidemiol Biomarkers Prev 2008;17:2480–2487.
14) Alagoz T, Buller RE, Berman M, Anderson B, Manetta A, DiSaia P. What is a normal CA125 level? Gynecol Oncol 1994;53:93-7.
15) Gadducci A, Cosio S, Carpi A ve ark. Serum tumor markers in the management of ovarian, endometrial and cervical cancer. Biomedecine & Pharmacotherapy 2004:58;24-38.