41 Non-invasive detection of endometrial cancer by DNA methylation analysis in urine size is being extended, together with paired cervicovaginal self-samples and clinician collected cervical scrapes to compare the diagnostic potential of DNA methylation analysis for EC detection in different sample types. We expect that a combination of present methylation markers with EC-specific markers could improve urine-based EC detection even further (33). Since EC is more common in older women with abnormal bleeding symptoms, it is important to note that the control subjects used in this study were slightly younger and information concerning abnormal bleeding symptoms was not documented. Therefore, the specificity of this approach remains to be determined in larger source populations that also include symptomatic and asymptomatic women at risk of EC, and women with benign endometrial lesions. CONCLUSIONS Our study demonstrates the feasibility of urine as a promising non-invasive specimen for EC detection. DNA methylation testing in urine could provide an attractive strategy for non-invasive EC detection for initial diagnosis during screening of asymptomatic women, to distinguish the minority of women presenting with postmenopausal bleeding symptoms due to underlying malignancy from those without EC, and to monitor women with an increased EC risk. Acknowledgements The authors would like to thank Birgit I. Lissenberg-Witte for her assistance in conducting the statistical analyses. Funding This research was funded by the Hanarth Foundation and Weijerhorst Foundation, who provided financial support for the conduct of the research and had no role in conducting the research and preparation of the manuscript. Ethics approval and consent to participate Ethical approval was obtained by the Medical Ethical Committee of the VU University Medical Center for both the SOLUTION1 study (no 2016.213) and the URIC biobank (no 2017.112). Each participant gave written informed consent upon recruitment. Availability of data and materials All data generated or analyzed during this study are available from the corresponding author on reasonable request. 2
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