Preoperative HE4, CA125 and ROMA in the differential diagnosis of benign and malignant adnexal masses

J Ovarian Res. 2016 Jul 19;9(1):43. doi: 10.1186/s13048-016-0254-7.


Background: The aim of this study was to evaluate HE4, CA125 and ROMA in the preoperative differentiation benign ovarian diseases from epithelial ovarian cancer depending on the menopausal status.

Methods: In order to estimate markers' concentrations in the serum of women with benign ovarian disease (n = 128) and with epithelial ovarian carcinoma (n = 96) the electrochemiluminescence (ECLIA) technique has been applied.

Results: Using the ROC analysis, although no statistical differences were found among their AUCs, the ROMA algorithm seems to be effective in gathering the diverse performance of HE4 and CA125. The AUC for HE4, CA125 and ROMA for all patients were: 0.895; 0.879 and 0.918, respectively. At established new optimal cutoff values for HE4, CA125 and ROMA we found higher specificity in postmenopausal compared to premenopausal women (96.9 vs 89.8 % and 97.7 vs 84.1 % and 95.9 vs 89.1 %, respectively). The sensitivity of HE4 in pre- and postmenopausal women was similar (83.5 vs 83.8 %), while for CA125 was the highest in premenopausal women (87.0 vs 84.1 %). For HE4, CA125 and ROMA the negative predictive value was high (97.6, 93.9 and 94.4 %, respectively).

Conclusions: The ROMA algorithm shows the best diagnostic performance to distinguish epithelial ovarian cancer from benign ovarian disease. We found the high specificity of HE4 and CA125 while differentiating ovarian benign diseases from epithelial ovarian cancer in postmenopausal women and the high sensitivity of CA125 in detecting epithelial ovarian cancer in premenopausal patients.

Keywords: CA125; HE4; Ovarian cancer; ROMA.

MeSH terms

  • Adnexal Diseases / blood*
  • Adnexal Diseases / diagnosis*
  • Adult
  • Aged
  • Aged, 80 and over
  • Algorithms*
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / blood
  • CA-125 Antigen / blood*
  • Diagnosis, Differential
  • Female
  • Humans
  • Membrane Proteins / blood*
  • Middle Aged
  • Postmenopause / blood
  • Premenopause / blood
  • Preoperative Period
  • Proteins / analysis*
  • WAP Four-Disulfide Core Domain Protein 2


  • Biomarkers, Tumor
  • CA-125 Antigen
  • MUC16 protein, human
  • Membrane Proteins
  • Proteins
  • WAP Four-Disulfide Core Domain Protein 2
  • WFDC2 protein, human