Serum HE4 as a prognostic marker in endometrial cancer : a population based study

Brennan, Donal J., Hackethal, Andreas, Metcalf, Alex M., Coward, Jermaine, Ferguson, Kaltin, Oehler, Martin, Quinn, Michael A., Janda, Monika, Leung, Yee, Freemantle, Michael, ANECS Group, Webb, Penelope M., Spurdle, Amanda B., & Obermair, Andreas (2014) Serum HE4 as a prognostic marker in endometrial cancer : a population based study. Gynecologic Oncology, 132(1), pp. 159-165.

View at publisher



HE4 has emerged as a promising biomarker in gynaecological oncology. The purpose of this study was to evaluate serum HE4 as a biomarker for high-risk phenotypes in a population-based endometrial cancer cohort.


Peri-operative serum HE4 and CA125 were measured in 373 patients identified from the prospective Australian National Endometrial Cancer Study (ANECS). HE4 and CA125 were quantified on the ARCHITECT instrument in a clinically accredited laboratory. Receiver operator curves (ROC), Spearman rank correlation coefficient, and chi-squared and Mann–Whitney tests were used for statistical analysis. Survival analysis was performed using Kaplan–Meier and Cox multivariate regression analyses.


Median CA125 and HE4 levels were higher in stage III and IV tumours (p < 0.001) and in tumours with outer-half myometrial invasion (p < 0.001). ROC analysis demonstrated that HE4 (area under the curve (AUC) = 0.76) was a better predictor of outer-half myometrial invasion than CA125 (AUC = 0.65), particularly in patients with low-grade endometrioid tumours (AUC 0.77 vs 0.64 for CA125). Cox multivariate analysis demonstrated that elevated HE4 was an independent predictor of recurrence-free survival (HR = 2.40, 95% CI 1.19–4.83, p = 0.014) after adjusting for stage and grade of disease, particularly in the endometrioid subtype (HR = 2.86, 95% CI 1.25–6.51, p = 0.012).


These findings demonstrate the utility of serum HE4 as a prognostic biomarker in endometrial cancer in a large, population-based study. In particular they highlight the utility of HE4 for pre-operative risk stratification to identify high-risk patients within low-grade endometrioid endometrial cancer patients who might benefit from lymphadenectomy.

Impact and interest:

18 citations in Scopus
Search Google Scholar™
19 citations in Web of Science®

Citation counts are sourced monthly from Scopus and Web of Science® citation databases.

These databases contain citations from different subsets of available publications and different time periods and thus the citation count from each is usually different. Some works are not in either database and no count is displayed. Scopus includes citations from articles published in 1996 onwards, and Web of Science® generally from 1980 onwards.

Citations counts from the Google Scholar™ indexing service can be viewed at the linked Google Scholar™ search.

Full-text downloads:

72 since deposited on 18 Feb 2014
28 in the past twelve months

Full-text downloads displays the total number of times this work’s files (e.g., a PDF) have been downloaded from QUT ePrints as well as the number of downloads in the previous 365 days. The count includes downloads for all files if a work has more than one.

ID Code: 67337
Item Type: Journal Article
Refereed: Yes
Keywords: Endometrial cancer, HE4, biomarker, prognostic marker
DOI: 10.1016/j.ygyno.2013.10.036
ISSN: 0090-8258
Subjects: Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000)
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Current > Schools > School of Public Health & Social Work
Copyright Owner: Copyright 2013 Elsevier Inc.
Copyright Statement: This is the author’s version of a work that was accepted for publication in Gynecologic Oncology. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Gynecologic Oncology, [VOL 132, ISSUE 1, (2014)] DOI: 10.1016/j.ygyno.2013.10.036
Deposited On: 18 Feb 2014 23:14
Last Modified: 02 Feb 2015 10:47

Export: EndNote | Dublin Core | BibTeX

Repository Staff Only: item control page