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Elevated plasma growth differentiation factor-15 correlates with lymph node metastases and poor survival in
Anne Cathrine Staff1, Jone Trovik, Ane Gerda Zahl Eriksson
1Department of Obstetrics and Gynecology, Oslo University Hospital, Ulleval, Norway. annetine.staff@uus.no
Purpose:
The study objective was to investigate and validate plasma growth differentiation factor-15 (GDF-15) as a predictor of lymph node metastasis and a poor prognosis in primary endometrial cancer.
Experimental Design:
Plasma samples from 510 women treated for endometrial cancer in a primary investigation cohort (n = 44) and a secondary validation cohort (n = 466) were analyzed for GDF-15. Plasma from healthy premenopausal (n = 20) and postmenopausal (n = 20) women, women with borderline (n = 43), benign (n = 144), and malignant ovarian tumors (n = 125) were used for comparison.
Results:
Median plasma GDF-15 concentration for the endometrial cancer group was elevated (1,077 ng/L) as compared with pre- and postmenopausal controls (590 and 684 ng/L) and women with benign (591 ng/L) or borderline ovarian tumors (718 ng/L; all P < 0.001), but similar to the ovarian cancer group. In the large validation cohort of endometrial carcinomas, high plasma GDF-15 was significantly associated with International Federation of Gynecology and Obstetrics (FIGO) stage III/IV disease, nonendometrioid histology, high grade, older age, postmenopausal status, and lymph node metastases (all P ≤ 0.001). High GDF-15 was also an independent predictor of poor disease-specific and recurrence-free survival.
Conclusions:
Based on findings indicated in a primary investigation set and confirmed in the large secondary validation set, we report for the first time plasma GDF-15 as a biomarker for endometrial cancer phenotype, including presence of lymph node metastasis and reduced survival. Its applicability as a predictor of metastatic nodes and in monitoring treatment of endometrial cancer needs to be further studied.
