title: Serum HE4 as a prognostic marker in endometrial cancer--a population based study.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Queensland Centre for Gynaecological Oncology, University of Queensland, School of Medicine, Central Clinical Division, Brisbane, Australia.
authors.forename: Donal J
authors.initials: DJ
authors.lastname: Brennan
authors.affiliation: Queensland Centre for Gynaecological Oncology, University of Queensland, School of Medicine, Central Clinical Division, Brisbane, Australia.
authors.forename: Andreas
authors.initials: A
authors.lastname: Hackethal
authors.affiliation: Queensland Institute of Medical Research, Genetics and Computational Biology Division, 300 Herston Rd, Herston, Brisbane 4006, Australia.
authors.forename: Alex M
authors.initials: AM
authors.lastname: Metcalf
authors.affiliation: Mater Medical Research Institute, South Brisbane, QLD, Australia.
authors.forename: Jermaine
authors.initials: J
authors.lastname: Coward
authors.affiliation: Queensland Institute of Medical Research, Genetics and Computational Biology Division, 300 Herston Rd, Herston, Brisbane 4006, Australia.
authors.forename: Kaltin
authors.initials: K
authors.lastname: Ferguson
authors.affiliation: Department of Gynaecological Oncology, Royal Adelaide Hospital, Adelaide, South Australia, Australia.
authors.forename: Martin K
authors.initials: MK
authors.lastname: Oehler
authors.affiliation: Women's Cancer Research Centre, Royal Women's Hospital, Victoria, Australia.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Quinn
authors.affiliation: School of Public Health, Queensland University of Technology, Brisbane, Australia.
authors.forename: Monika
authors.initials: M
authors.lastname: Janda
authors.affiliation: School of Women's and Infants' Health, University of Western Australia, Perth, Australia.
authors.forename: Yee
authors.initials: Y
authors.lastname: Leung
authors.affiliation: Sullivan Nicolaides Pathology, Cnr Whitmore St & Seven Oaks St, Taringa, QLD 4068, Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Freemantle
authors.affiliation: Queensland Institute of Medical Research, Genetics and Computational Biology Division, 300 Herston Rd, Herston, Brisbane 4006, Australia.
authors.forename: Penelope M
authors.initials: PM
authors.lastname: Webb
authors.affiliation: Queensland Institute of Medical Research, Genetics and Computational Biology Division, 300 Herston Rd, Herston, Brisbane 4006, Australia.
authors.forename: Amanda B
authors.initials: AB
authors.lastname: Spurdle
authors.affiliation: Queensland Centre for Gynaecological Oncology, University of Queensland, School of Medicine, Central Clinical Division, Brisbane, Australia. Electronic address: ao@surgicalperformance.com.
authors.forename: Andreas
authors.initials: A
authors.lastname: Obermair
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood*; D018394:CA-125 Antigen / Q000097:blood; D016889:Endometrial Neoplasms / Q000097:blood* / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D011506:Proteins / Q000032:analysis*; 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
keywords: Biomarker; Endometrial cancer; HE4; Prognostic marker