title: Growth differentiation factor-15 as biomarker in uterine sarcomas.
abstract: 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.
  
  
  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.
authors.affiliation: *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.
authors.forename: Jone
authors.initials: J
authors.lastname: Trovik
authors.forename: Helga Birgitte
authors.initials: HB
authors.lastname: Salvesen
authors.forename: Tine
authors.initials: T
authors.lastname: Cuppens
authors.forename: Frederic
authors.initials: F
authors.lastname: Amant
authors.forename: Anne Cathrine
authors.initials: AC
authors.lastname: Staff
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood*; D016022:Case-Control Studies; D005260:Female; D055436:Growth Differentiation Factor 15 / Q000097:blood*; D006801:Humans; D007889:Leiomyoma / Q000097:blood*; D008875:Middle Aged; D012509:Sarcoma / Q000097:blood*; D014594:Uterine Neoplasms / Q000097:blood*; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C526140:GDF15 protein, human; D055436:Growth Differentiation Factor 15