About CA125 + HE4

Clinical Data

Know the right treatment path.

5% to 10% of women in the
United States will have a suspected pelvic mass and undergo surgery in their lifetimes. Of these women, only 13% to 21% will have an ovarian cancer diagnosis.13

The Use of Multiple Novel Tumor Biomarkers for the Detection of Ovarian Carcinoma in Patients with a Pelvic Mass. Gynecologic Oncology. 108(2); 402-408. (2008) Richard G. Moore et al.

A Novel Multiple Marker Bioassay Utilizing HE4 and CA125 for the Prediction of Ovarian Cancer in Patients with a Pelvic Mass. Gynecologic Oncology. 112 (1): 40-46. (2009) Richard Ge. Moore et al.

Multiple Novel Biomarkers for the Detection of Ovarian Cancer

In a 2007 prospective trial examining the use of multiple novel biomarkers and the creation of a multiple marker assay to detect ovarian cancer in women presenting with pelvic mass, 259 patients with adnexal masses were enrolled. Of these, 233 were eligible for analysis with 67 invasive epithelial ovarian cancers and 166 benign ovarian neoplasms.


  • Mean values for all marker levels except HER-2/neu differed significantly between patients with benign masses and cancer
  • As a single marker, HE4 had the highest sensitivity at 72.9% (specificity 95%)
  • Combined, CA125™ and HE4 yielded the highest sensitivity at 76.4% (specificity 95%)
  • The combination of CA125 and HE4 added 33.1% to the sensitivity of CA125 alone and 3.5% to the sensitivity of HE4 alone
  • Additional markers added only minimally to the sensitivity of the CA125 and HE4 combination
  • HE4 was the best single marker for Stage I disease, with no increase in sensitivity when combined with CA125 or any other marker

As a single tumor marker, HE4 had the highest sensitivity for detecting ovarian cancer, especially Stage I disease. Combined, CA125 and HE4 is a more accurate predictor of malignancy than either is alone.9

Other biomarkers analyzed were soluble mesothelin-related peptide (SMRP), CA72-4®, activin A, inhibin, osteopontin, epidermal growth factor receptor (EGFR), and serum HER-2/neu. All tumor marker levels were compared with the final pathologic diagnosis. The addition of osteopontin or inhibin to HE4 did increase the sensitivity of HE4 alone (to 73.1% or 74.4%, respectively), but the increase in sensitivity did not exceed that of the HE4 and CA125 combination (76.4%).9

The analysis of multiple biomarker combinations (3 or more) added only a small percentage to the sensitivity of combined CA125 and HE4.9

View the full study on multiple biomarkers in ovarian cancer

View a selection of CA125 + HE4 clinical studies

Novel Marker Assay, CA125 and HE4 for the Prediction of Ovarian Cancer

In 2008, a prospective multicenter trial was conducted to validate the predictive model using HE4 and CA125 to assess the risk of epithelial ovarian cancer (EOC) in women presenting with a pelvic mass. For this study, 566 patients were enrolled from 12 different geographic sites. Of these, 531 were evaluable, with 283 postmenopausal women and 248 premenopausal women.23

Analysis of serum tumor marker levels was performed for all patients as a group and for postmenopausal and premenopausal patients as separate groups.


  • The dual marker algorithm stratified patients into low- and high-risk malignancy groups using the designated predictive probability thresholds for premenopausal and postmenopausal women
  • The high-risk group was defined as a predictive probability of >13.1% for premenopausal women and >27.7% for postmenopausal women
  • The study demonstrated that the Risk of Ovarian Malignancy Algorithm, or ROMA™, successfully classified patients, with 88.7% of EOC and low malignant potential tumors correctly classified as high risk
  • The negative predictive value (NPV) in the total population studied was 93.9%, meaning the test achieved a false negative rate of 6% in the combined patient population
  • Of 129 patients with EOC, 121 (93.8%) were correctly classified into the high-risk group
  • The combination of HE4 and CA125, or HE4 alone, has greater sensitivity in patients with early-stage disease than CA125 alone9

The dual marker combination of HE4 and CA125 using ROMA can help classify women into high- and low-risk groups, allowing for the effective triage of women to appropriate surgical centers for their care.

The CA125 + HE4 risk stratification test, utilizing ROMA, is CE marked and available for clinical use. For ordering information, please contact your laboratorian.

View the full study on the HE4 and CA125 multiple marker assay

View a selection of CA125 + HE4 clinical studies


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