The use of multiple novel tumor biomarkers for the detection of ovarian carcinoma in patients with a pelvic mass

Gynecol Oncol. 2008 Feb;108(2):402-8. doi: 10.1016/j.ygyno.2007.10.017. Epub 2007 Dec 3.


Objectives: The CA125 tumor marker is used to help predict the presence of ovarian cancer in patients with an adnexal mass. Because elevated CA125 levels occur in many benign gynecologic conditions, we set out to identify other novel biomarkers that would increase the sensitivity and specificity of CA125.

Methods: Serum and urine samples were obtained preoperatively from women undergoing surgery for an adnexal mass. The samples were analyzed for levels of CA125, SMRP, HE4, CA72-4, activin, inhibin, osteopontin, epidermal growth factor (EGFR), and ERBB2 (Her2) and were compared to final pathology results. Logistic regression models were estimated for all markers and combinations, with cross-validation analysis performed to obtain the sensitivities at set specificities of 90%, 95%, and 98%.

Results: Two hundred and fifty-nine patients with adnexal masses were enrolled. Of these, 233 patients were eligible for analysis with 67 invasive epithelial ovarian cancers and 166 benign ovarian neoplasms. Mean values for all marker levels except Her2 differed significantly between patients with benign masses and cancer. As a single marker, HE4 had the highest sensitivity at 72.9% (specificity 95%). Comparatively, combined CA125 and HE4 yielded the highest sensitivity at 76.4% (specificity 95%), with additional markers adding minimally to the sensitivity of this combination. HE4 was the best single marker for Stage I disease, with no increase in sensitivity when combined with CA125 or any other marker.

Conclusions: 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 alone.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adnexa Uteri / pathology
  • Aged
  • Biomarkers, Tumor / blood*
  • Biomarkers, Tumor / urine*
  • CA-125 Antigen / blood
  • CA-125 Antigen / urine
  • Epididymal Secretory Proteins / metabolism
  • Female
  • Humans
  • Middle Aged
  • Ovarian Neoplasms / blood*
  • Ovarian Neoplasms / pathology
  • Ovarian Neoplasms / urine*
  • Pelvic Neoplasms / blood*
  • Pelvic Neoplasms / pathology
  • Pelvic Neoplasms / urine*
  • Prospective Studies
  • Sensitivity and Specificity
  • beta-Defensins


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