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Growth differentiation factor-15 as biomarker in uterine sarcomas
Jone Trovik1, Helga Birgitte Salvesen, Tine Cuppens
1*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.
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.
