Abstract
Simple SummaryThere are currently no blood biomarkers approved for routine clinical use in endometrial cancer. Serum human epididymis protein 4 (HE4) is significantly higher in patients with endometrial cancer compared to patients without endometrial cancer and is associated with a poorer prognosis. This makes HE4 an attractive candidate for clinical use in endometrial cancer. The aim of this review is to summarise the evidence for the use of serum HE4 in the detection, prognosis, prediction of therapy response and recurrence monitoring in endometrial cancer. The utility of combining HE4 with other biomarkers or imaging and clinical variables, and its detection in other biofluids is also discussed, as well as potential challenges for clinical use and recommended areas for future research.There are currently no blood biomarkers in routine clinical use in endometrial carcinoma (EC). Human epididymis protein 4 (HE4) is a glycoprotein that is overexpressed in the serum of patients with EC, making it a good candidate for use as a diagnostic and/or prognostic biomarker. HE4 is correlated with poor prognostic factors, including stage, myometrial invasion and lymph node metastases, which means it could be used to guide decisions regarding the extent of surgery and need for adjuvant therapy. Serum HE4 has also shown promise for predicting responses to progestin therapy in early-stage EC. The use of algorithms and indices incorporating serum HE4 and other biomarkers, including clinical and imaging variables, is an area of increasing interest. Serum HE4 levels rise with age and renal dysfunction, which may affect the interpretation of results. This review covers the evidence supporting the use of HE4 as an EC biomarker for diagnosis, prognosis, recurrence monitoring, and prediction of therapy response. The evidence for combining serum HE4 with other biomarkers, including clinical and imaging variables, its value as a biomarker in other biofluids and potential challenges of its clinical use are also discussed.
Highlights
Endometrial carcinoma (EC) is the most common gynaecological malignancy
The aim of this review is to summarise the evidence supporting the role of Human epididymis protein 4 (HE4) as a diagnostic, prognostic and predictive biomarker for EC, both alone and in combination with other biomarkers, and its potential utility in clinical practice
Orbo et al showed a greater proportion of patients with hyperplasia who responded to progesterone therapy displayed a reduction in endometrial tissue HE4 expression at six months compared to those that did not respond (53% vs. 6%)
Summary
Endometrial carcinoma (EC) is the most common gynaecological malignancy. Its incidence has risen by 55% over the last 30 years, with the death rate increasing by 23% [1]. This includes women with class III obesity (body mass index > 40 kg/m2) and/or medical co-morbidities with high risk of surgical morbidity and mortality, and those wishing to preserve fertility In these cases, women are managed with primary radiotherapy or hormone therapy with progestin. A prognostic biomarker could help risk stratify women with EC to aid surgical planning, decisions about adjuvant treatment, follow up programmes and monitoring for recurrence, creating a more personalised approach to management. A predictive biomarker could help guide decisions regarding systemic therapy, such as conservative management with progestin in early-stage EC These important clinical uses have been identified by clinicians, and by EC patients and carers as areas worthy of further development in our recent James Lind Alliance research gap analysis [10,11]. Original clinical research articles and meta-analyses were used for data extraction
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