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Gynecol Oncol. 2013 Jun;129(3):467-71. doi: 10.1016/j.ygyno.2013.03.001. Epub 2013 Mar 13.

Differentiating stage 1 epithelial ovarian cancer from benign ovarian tumours using a combination of tumour markers HE4, CA125, and CEA and patient's age.

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  • 1Rural Clinical School, School of Medicine, The University of Queensland, Australia.



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.


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.


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%.


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.

Copyright © 2013 Elsevier Inc. All rights reserved.

[PubMed - indexed for MEDLINE]
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