Growth Differentiation Factor-15 as Biomarker in Uterine Sarcomas

Trovik, Jone MD, PhD*†; Salvesen, Helga Birgitte MD, PhD*†; Cuppens, Tine MSc; Amant, Frederic MD, PhD§; Staff, Anne Cathrine MD, PhD∥¶

International Journal of Gynecological Cancer: February 2014 - Volume 24 - Issue 2 - p 252–259
doi: 10.1097/IGC.0000000000000037
Uterine Cancer

Objective: The aim of this study was to investigate and validate circulating growth differentiation factor-15 (GDF-15) as a discriminating biomarker between highly malignant uterine sarcomas and benign uterine leiomyomas. In addition, we investigated whether GDF-15 differed between uterine sarcomas and benign adnexal tumors, ovarian or endometrial cancer, and borderline tumors of the ovary.

Materials and Methods: Preoperative blood samples from 19 women with a diagnosis of uterine sarcoma were analyzed for GDF-15 with immunoassay and compared with samples from 50 patients operated on for leiomyoma uteri and with samples from 20 premenopausal and 20 postmenopausal controls. Our previously presented preoperative GDF-15 concentrations in women with borderline (n = 43), benign (n = 144), and malignant ovarian tumors (n = 125), as well as endometrial cancer (n = 510), were used for comparison.

Results: The median circulating GDF-15 concentration was elevated in the uterine sarcoma group (943 ng/L) compared with the myoma uteri group (647 ng/L), the premenopausal and postmenopausal controls (363 and 545 ng/L), and the women with benign ovarian tumors (591 ng/L, all P ≤ 0.007) but was not significantly different from the ovarian borderline tumor (718 ng/L) or ovarian (1242 ng/L) or endometrial cancer (1076 ng/L) groups.

High GDF-15 levels were significantly associated with leiomyosarcomas (P = 0.036), advanced disease (International Federation of Gynecology and Obstetrics stage III/IV, P = 0.013), large tumors (≥10 cm, P = 0.009), and poor survival (P = 0.022).

Conclusions: Circulating GDF-15 may be a promising novel biomarker for the preoperative identification of malignant pelvic disease. Further large prospective studies are needed to evaluate the clinical usefulness of GDF-15 as a discriminator between benign leiomyomas and aggressive sarcomas and as a marker to guide surgical and systemic therapy.

*Department of Obstetrics and Gynecology, Haukeland University Hospital, and †Department of Clinical Medicine, The University of Bergen, Bergen, Norway; ‡Gynecologic Oncology, University Hospitals Leuven, Leuven, Belgium; §Gynecologic Oncology, University Hospitals Leuven & Department of Oncology, KU Leuven, Leuven, Belgium; ∥Department of Gynecology, Oslo University Hospital, Ulleval, and ¶Faculty of Medicine, University of Oslo, Oslo, Norway.

Address correspondence and reprint requests to Jone Trovik, MD, PhD, Department of Obstetrics and Gynecology, Haukeland University Hospital, Jonas Liesv 72, 5021 Hakeland Hospital, Bergen, Norway. E-mail: Jone.Trovik@helse-bergen.no; Jone.Trovik@med.uib.no.

Jone Trovik has been supported by Helse Vest Research Fund no. 911371 as a PhD research fellow. Anne Cathrine Staff has received funding from Oslo University Hospital. Helga Salvesen has received funding from the Norwegian Research Council, The University of Bergen, The Meltzer Foundation, and The Norwegian Cancer Society (The Harald Andersen’s legacy).

Frederic Amant is a senior clinical researcher at the Flandern Research Foundation (F.W.O.).

The authors declare no conflicts of interest.

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Received September 2, 2013

Received in revised form October 11, 2013

Accepted October 17, 2013

© 2014 by the International Gynecologic Cancer Society and the European Society of Gynaecological Oncology.