Serum HE4 detects recurrent endometrial cancer in patients undergoing routine clinical surveillance

Brennan, Donal J, Hackethal, Andreas, Mann, Kristy P, Mutz-Dehbalaie, Irene, Fiegl, Heidi, Marth, Christian and Obermair, Andreas (2015) Serum HE4 detects recurrent endometrial cancer in patients undergoing routine clinical surveillance. BMC Cancer, 15 33: . doi:10.1186/s12885-015-1028-0

Author Brennan, Donal J
Hackethal, Andreas
Mann, Kristy P
Mutz-Dehbalaie, Irene
Fiegl, Heidi
Marth, Christian
Obermair, Andreas
Title Serum HE4 detects recurrent endometrial cancer in patients undergoing routine clinical surveillance
Journal name BMC Cancer   Check publisher's open access policy
ISSN 1471-2407
Publication date 2015-02-06
Year available 2015
Sub-type Article (original research)
DOI 10.1186/s12885-015-1028-0
Open Access Status DOI
Volume 15
Issue 33
Total pages 9
Place of publication London, United Kingdom
Publisher BioMed Central Ltd.
Language eng
Formatted abstract

The purpose of this study was to evaluate serum HE4 as a biomarker to detect recurrent disease during follow-up of patients with endometrial adenocarcinoma (EAC).


We performed a retrospective analysis of 98 EAC patients treated at Innsbruck Medical University, between 1999 and 2009. Twenty-six patients developed recurrent disease. Median follow-up was 5 years. Serum HE4 and CA125 levels were analyzed using the ARCHITECT assay (Abbott, Wiesbaden, Germany) pre-operatively (baseline), post-operative (interval) and after histological confirmation of recurrent disease or when patients returned for clinical review with no evidence of recurrent disease (recurrence/final)). Receiver operator curves (ROC), Spearman rank correlation coefficient, chi-squared and Mann–Whitney tests were used for statistical analysis.


HE4 levels decreased after initial treatment (p = 0.001) and increased again at recurrence (p = 0.002). HE4 was elevated (>70 pmol/L) in 21 of 26 (81%) and CA125 was elevated (>35 U/ml) in 12 of 26 (46%) patients at recurrence. In endometrioid histology (n = 69) serum HE4 measured during follow up (Area under the curve (AUC) = 0.87, 95%CI 0.79-0.95) was a better indicator of recurrence than CA125 (AUC = 0.67, 95%CI 0.52-0.83). A HE4 level of 70 pmol/L was associated with a sensitivity of 84%, a specificity of 74% and a negative predictive value of 93% when assessing for recurrent endometrioid EAC.

This is a preliminary description of HE4 serum levels measured during routine follow up of EAC patients. Serum HE4 measured during clinical follow-up may identify recurrent disease particularly in patients with endometrioid histology. Further prospective validation of HE4 is warranted.
Keyword Endometrial cancer
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
School of Medicine Publications
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