GDF-15 in Endometrial Cancer 1 Elevated Plasma Growth Differentiation Factor-15 Correlates with Lymph Node Metastases and Poor Survival in Endometrial Cancer

Purpose: The study objective was to investigate and validate plasma Growth Differentiation Factor-15 (GDF-15) as predictor of lymph node metastasis and 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 (1077 ng/L) as compared to preand 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 FIGO stage III/IV disease, non-endometrioid histology, high grade, high age, postmenopausal status and lymph node metastases (all P-values ≤ 0.001). High GDF-15 was also an independent predictor of poor disease-specific and recurrence-free survival. Conclusion: 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 predictor of metastatic nodes and in monitoring treatment of endometrial cancer needs to be further studied. Research. on April 12, 2017. © 2011 American Association for Cancer clincancerres.aacrjournals.org Downloaded from Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on May 26, 2011; DOI: 10.1158/1078-0432.CCR-11-0715