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

Ulla-Maija Haltia; Marianne Hallamaa; Johanna Tapper; Johanna Hynninen; Henrik Alfthan; Bhanu Kalra; Olli Ritvos; Markku Heikinheimo; Leila Unkila-Kallio; Antti Perheentupa; Anniina Färkkilä

doi:10.1016/j.ygyno.2016.11.018

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.

Authors

Affiliations

¹ Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, PO Box 20, 00014, University of Helsinki, Finland; Children's Hospital, University of Helsinki and Helsinki University Hospital, PO Box 20, 00014, University of Helsinki, Finland.
² Department of Obstetrics and Gynecology, University of Turku and Turku University Hospital, 20520 Turku, Finland.
³ Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, PO Box 20, 00014, University of Helsinki, Finland.
⁴ Clinical Chemistry, University of Helsinki and HUSLAB, Finland.
⁵ AnshLabs, Webster, TX, USA.
⁶ Physiology, Faculty of Medicine, University of Helsinki, Finland.
⁷ Children's Hospital, University of Helsinki and Helsinki University Hospital, PO Box 20, 00014, University of Helsinki, Finland; Department of Pediatrics, St. Louis Children´s Hospital, Washington University School of Medicine, St. Louis, MO 63110, USA.
⁸ Department of Obstetrics and Gynecology, University of Turku and Turku University Hospital, 20520 Turku, Finland; Department of Physiology, Institute of Biomedicine, University of Turku, 20014 Turku, Finland.
⁹ Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, PO Box 20, 00014, University of Helsinki, Finland; Children's Hospital, University of Helsinki and Helsinki University Hospital, PO Box 20, 00014, University of Helsinki, Finland. Electronic address: Anniina.farkkila@helsinki.fi.

PMID: 27871721
DOI: 10.1016/j.ygyno.2016.11.018

Abstract

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

Substances

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