Roles of human epididymis protein 4, carbohydrate antigen 125, inhibin B and anti-Müllerian hormone in the differential diagnosis and follow-up of ovarian granulosa cell tumors

Gynecol Oncol. 2017 Jan;144(1):83-89. doi: 10.1016/j.ygyno.2016.11.018. Epub 2016 Nov 18.


Objective: Evaluation of circulating tumor markers in ovarian cancer is crucial for optimal patient care. The goal of this study was to verify the most accurate circulating tumor markers for the diagnosis and follow-up of adult-type granulosa cell tumors (AGCTs).

Methods: The levels of circulating human epididymis protein 4 (HE4) and carbohydrate antigen 125 (CA125), together with AGCT markers inhibin B and anti-Müllerian hormone (AMH), were measured in 135 samples from AGCT patients, 37 epithelial ovarian carcinoma (EOC) patients, and 40 endometrioma (ENDO) patients. The levels were plotted with receiver operating characteristic (ROC) graphs, and the area under the curves (AUC) of the different markers were calculated and compared.

Results: HE4 levels were significantly lower in AGCTs than in EOCs (p<0.0001). CA125 levels were above 35IU/l in 25% of AGCT patients and 47.5% of ENDO patients, whereas inhibin B and AMH levels were elevated only in patients with AGCTs. In the AUC comparison analyses, inhibin B alone was sufficient to differentiate AGCT from EOC. In differentiating AGCT from ENDO, inhibin B and AMH performed similarly, and the combination of inhibin B and AMH increased the accuracy compared to either marker alone (sensitivity, 100%; specificity, 93%). Among AGCT patients, inhibin B was the best marker for detecting the presence of AGCT.

Conclusions: HE4 and CA125 levels were low in AGCTs, and inhibin B was the most accurate circulating biomarker in distinguishing AGCTs from EOCs and from ENDOs. Inhibin B was also the best single marker for AGCT follow-up.

Keywords: AMH; CA125; Granulosa cell tumor; HE4; Inhibin B; Ovarian cancer.

MeSH terms

  • Adult
  • Aftercare
  • Aged
  • Aged, 80 and over
  • Anti-Mullerian Hormone / blood
  • Area Under Curve
  • Biomarkers, Tumor / blood*
  • CA-125 Antigen / blood
  • Diagnosis, Differential
  • Endometriosis / blood*
  • Endometriosis / diagnosis*
  • Female
  • Granulosa Cell Tumor / blood*
  • Granulosa Cell Tumor / diagnosis*
  • Humans
  • Inhibins / blood
  • Middle Aged
  • Neoplasms, Glandular and Epithelial / blood*
  • Neoplasms, Glandular and Epithelial / diagnosis*
  • Proteins / metabolism
  • ROC Curve
  • WAP Four-Disulfide Core Domain Protein 2


  • Biomarkers, Tumor
  • CA-125 Antigen
  • Proteins
  • WAP Four-Disulfide Core Domain Protein 2
  • WFDC2 protein, human
  • inhibin B
  • Inhibins
  • Anti-Mullerian Hormone

Supplementary concepts

  • Granulosa cell tumor of the ovary