title: Serum HE4 detects recurrent endometrial cancer in patients undergoing routine clinical surveillance.
abstract: BACKGROUND
  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).
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Queensland Centre for Gynaecological Oncology, University of Queensland, School of Medicine, Central Clinical Division, Brisbane, Australia. donal.brennan@mac.com.
authors: Donal J
authors: DJ
authors: Brennan
authors: Queensland Centre for Gynaecological Oncology, University of Queensland, School of Medicine, Central Clinical Division, Brisbane, Australia. hackvalley@me.com.
authors: Andreas
authors: A
authors: Hackethal
authors: NHMRC Clinical Trials Centre, University of Sydney, Sydney, NSW, Australia. kristy.mann@ctc.usyd.edu.au.
authors: Kristy P
authors: KP
authors: Mann
authors: Department of Obstetrics and Gynecology, Innsbruck Medical University, Innsbruck, Austria. Irene.Mutz-Dehbalaie@i-med.ac.at.
authors: Irene
authors: I
authors: Mutz-Dehbalaie
authors: Department of Obstetrics and Gynecology, Innsbruck Medical University, Innsbruck, Austria. Heidelinde.Fiegl@i-med.ac.at.
authors: Heidi
authors: H
authors: Fiegl
authors: Department of Obstetrics and Gynecology, Innsbruck Medical University, Innsbruck, Austria. Christian.MARTH@uki.at.
authors: Christian
authors: C
authors: Marth
authors: Queensland Centre for Gynaecological Oncology, University of Queensland, School of Medicine, Central Clinical Division, Brisbane, Australia. ao@surgicalperformance.com.|Queensland Centre for Gynaecological Oncology, Royal Brisbane and Womens Hospital, Ned Hanlon Building, Herston, QLD, 4006, Australia. ao@surgicalperformance.com.
authors: Andreas
authors: A
authors: Obermair
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood*; D018394:CA-125 Antigen / Q000097:blood; D016889:Endometrial Neoplasms / Q000097:blood* / Q000473:pathology* / Q000628:therapy; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D011506:Proteins; D012372:ROC Curve; D012189:Retrospective Studies; D016896:Treatment Outcome; D000081102:WAP Four-Disulfide Core Domain Protein 2
chemical_list: D014408:Biomarkers, Tumor; D018394:CA-125 Antigen; D011506:Proteins; D000081102:WAP Four-Disulfide Core Domain Protein 2; C569698:WFDC2 protein, human
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