A novel multiple marker bioassay utilizing HE4 and CA125 for the prediction of ovarian cancer in patients with a pelvic mass

Gynecol Oncol. 2009 Jan;112(1):40-6. doi: 10.1016/j.ygyno.2008.08.031. Epub 2008 Oct 12.


Introduction: Patients diagnosed with epithelial ovarian cancer (EOC) have improved outcomes when cared for at centers experienced in the management of EOC. The objective of this trial was to validate a predictive model to assess the risk for EOC in women with a pelvic mass.

Methods: Women diagnosed with a pelvic mass and scheduled to have surgery were enrolled on a multicenter prospective study. Preoperative serum levels of HE4 and CA125 were measured. Separate logistic regression algorithms for premenopausal and postmenopausal women were utilized to categorize patients into low and high risk groups for EOC.

Results: Twelve sites enrolled 531 evaluable patients with 352 benign tumors, 129 EOC, 22 LMP tumors, 6 non EOC and 22 non ovarian cancers. The postmenopausal group contained 150 benign cases of which 112 were classified as low risk giving a specificity of 75.0% (95% CI 66.9-81.4), and 111 EOC and 6 LMP tumors of which 108 were classified as high risk giving a sensitivity of 92.3% (95% CI=85.9-96.4). The premenopausal group had 202 benign cases of which 151 were classified as low risk providing a specificity of 74.8% (95% CI=68.2-80.6), and 18 EOC and 16 LMP tumors of which 26 were classified as high risk, providing a sensitivity of 76.5% (95% CI=58.8-89.3).

Conclusion: An algorithm utilizing HE4 and CA125 successfully classified patients into high and low risk groups with 93.8% of EOC correctly classified as high risk. This model can be used to effectively triage patients to centers of excellence.

Trial registration: ClinicalTrials.gov NCT00315692.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Algorithms
  • Biomarkers, Tumor / blood*
  • CA-125 Antigen / blood*
  • Epididymal Secretory Proteins / metabolism*
  • Female
  • Humans
  • Logistic Models
  • Middle Aged
  • Ovarian Neoplasms / blood*
  • Ovarian Neoplasms / diagnosis
  • Ovarian Neoplasms / surgery
  • Pelvic Neoplasms / blood*
  • Pelvic Neoplasms / diagnosis
  • Pelvic Neoplasms / surgery
  • Predictive Value of Tests
  • Prospective Studies
  • beta-Defensins


  • Biomarkers, Tumor
  • CA-125 Antigen
  • DEFB126 protein, human
  • Epididymal Secretory Proteins
  • beta-Defensins

Associated data

  • ClinicalTrials.gov/NCT00315692