Comparison of ovarian cancer markers in endometriosis favours HE4 over CA125

Brett Mckinnon, Michael D Mueller, Konstantinos Nirgianakis, Nick A Bersinger
Molecular medicine reports · 2015 · vol. 12(4) , pp. 5179–5184 · doi:10.3892/mmr.2015.4062 · PMID:26165164 · W2141825956
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⚙ AI-generated summary by claude@2026-06, 2026-06-08 ⓘ

This study found that HE4 levels in peritoneal fluid are increased in endometriosis patients, are less affected by hormonal treatment and menstrual cycle phase, and thus show greater potential as an ovarian cancer risk marker than CA125.

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⚙ AI-generated deep summary by claude@2026-06, 2026-06-09 ⓘ

This study measured human epididymis protein 4 (HE4) and CA125 in peritoneal fluid from 258 women with endometriosis and 100 control women without endometriosis, using ELISA on samples collected at laparoscopy in Bern, Switzerland, between 2007 and 2014, while stratifying patients by prior hormonal treatment and menstrual cycle phase. Both markers were significantly increased in untreated endometriosis compared with controls, but hormone treatments (combined oral contraceptives, continuous gestagens, or GnRH agonists) normalized CA125 to control levels while reducing HE4 to below control levels; additionally, CA125 differed by proliferative versus secretory cycle phase whereas HE4 did not. A key limitation noted is the large patient-to-patient variability (up to several orders of magnitude) and the handling of values below detection limits by imputation. This paper is centrally about endometriosis — it compares peritoneal HE4 versus CA125 and evaluates how hormonal treatment and menstrual cycle phase affect them in women with endometriosis.

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Abstract

Endometriosis is a gynaecological condition with an associated chronic inflammatory response. The ectopic growth of 'lesions', consisting of endometrial cells outside the uterine cavity, stimulates an inflammatory response initiating the activation of macrophages, and resulting in increased cytokine and growth factor concentrations in the peritoneal fluid (PF). Endometriosis‑associated inflammation is chronic and long lasting. In patients with endometriosis, the risk of developing ovarian cancer within 10 years, particularly of the endometrioid or clear cell subtype, is increased 2.5‑4 times. Endometriosis creates a peritoneal environment that exposes the affected endometriotic and the normal ovarian surface epithelial cells to agents that have been suggested to be involved in the pathogenesis of cancer. Concentrations of several cytokines and growth factors were increased in the PF of patients with endometriosis. The ovarian cancer marker, CA125, was one such growth factor; however, this remains to be confirmed. Human epididymis protein 4 (HE4) was detected at high concentrations in patients with ovarian cancer and was identified as the best biomarker for the detection of ovarian cancer. The present study determined the levels of HE4 and CA125 in the peritoneal fluid of 258 patients with and 100 control individuals without endometriosis attending the Department of Obstetrics and Gynaecology, University of Berne (Berne, Switzerland) between 2007 and 2014. The cases were subdivided into groups without hormonal treatment (n=107), or treated with combined oral contraceptives (n=45), continuous gestagens (n=56) or GnRH agonists (n=50). Both of these markers were significantly increased in the non‑treated endometriosis samples compared with the control group. Hormone treatment with either of the three agents mentioned resulted in the concentration of CA125 returning to the control levels and the concentration of HE4 decreasing to below the control levels. CA125, however not HE4, significantly differed between the proliferative and secretory cycle phases. Since HE4 is sensitive to hormonal treatment and robust towards menstrual cycle variation, HE4 is potentially superior to CA125 as an endometriosis marker and therefore has greater potential as a marker for the identification of women at risk of developing ovarian cancer.

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Condition tags

endometriosis

MeSH descriptors

CA-125 Antigen Endometriosis Endometriosis Ovarian Neoplasms Ovarian Neoplasms Proteins Adult Biomarkers CA-125 Antigen Endometriosis Endometriosis Endometriosis Enzyme-Linked Immunosorbent Assay Female Humans Ovarian Neoplasms Ovarian Neoplasms Proteins Risk Factors WAP Four-Disulfide Core Domain Protein 2

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