title: Differentiating stage 1 epithelial ovarian cancer from benign ovarian tumours using a combination of tumour markers HE4, CA125, and CEA and patient's age.
abstract: OBJECTIVE
  Evaluating the presence of possible malignant disease in women with ovarian masses relies on medical imaging and serum marker findings. This study considers the role of serum Human Epididymal Protein 4 (HE4) antigen in combination with other serum markers to more effectively estimate the risk of malignancy in patients with isolated pelvic masses.
  
  
  METHODS
  We used prospectively collected biospecimens held by the Australian Ovarian Cancer Study (AOCS). Serum samples of patients with FIGO stage 1 epithelial ovarian cancer or with a benign condition were analysed for levels of circulating HE4 antigen, CA 125, and CEA, and test results were used to predict the presence of malignancy and to differentiate benign from malignant pelvic masses.
  
  
  RESULTS
  HE4 levels were significantly elevated amongst postmenopausal women and amongst patients with malignancy compared to premenopausal women and those with benign disease (p<0.001 for both). The combination of CA125 and age, achieved an area under the ROC curve of 0.677 (95% CI: 0.584 to 0.770, p=0.778), whilst HE4+CA125+CEA in combination with patient's age showed significantly higher AUC of 0.797 (95% CI: 0.721 to 0.874, p=0.0052). By adjusting the ROMA cut-off values the percentage of correctly classified premenopausal patients into low and high risk groups increased from 36.99% to 69.86%.
  
  
  CONCLUSIONS
  In patients with isolated pelvic masses, the combination of HE4, CA 125 and age with or without CEA provides higher diagnostic value compared to CA125 and age alone. It may therefore be considered for continuous evaluation in patients with adnexal masses.
authors.affiliation: Rural Clinical School, School of Medicine, The University of Queensland, Australia.
authors.forename: Srinivas
authors.initials: S
authors.lastname: Kondalsamy-Chennakesavan
authors.forename: Andreas
authors.initials: A
authors.lastname: Hackethal
authors.forename: David
authors.initials: D
authors.lastname: Bowtell
authors.forename: Andreas
authors.initials: A
authors.lastname: Obermair
mesh_terms: D000367:Age Factors; D014408:Biomarkers, Tumor / Q000097:blood*; D018394:CA-125 Antigen / Q000097:blood; D002272:Carcinoembryonic Antigen / Q000097:blood; D000077216:Carcinoma, Ovarian Epithelial; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D008565:Membrane Proteins / Q000097:blood; D008875:Middle Aged; D009367:Neoplasm Staging; D009375:Neoplasms, Glandular and Epithelial / Q000097:blood / Q000175:diagnosis* / Q000473:pathology; D010049:Ovarian Diseases / Q000097:blood / Q000175:diagnosis* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000473:pathology; D011446:Prospective Studies; D011506:Proteins / Q000378:metabolism; D000081102:WAP Four-Disulfide Core Domain Protein 2
chemical_list: D014408:Biomarkers, Tumor; D018394:CA-125 Antigen; D002272:Carcinoembryonic Antigen; C451759:MUC16 protein, human; D008565:Membrane Proteins; D011506:Proteins; D000081102:WAP Four-Disulfide Core Domain Protein 2; C569698:WFDC2 protein, human