Analysis of uterine lavage for early ovarian cancer detection

Introduction/Background Ovarian cancer (OC) has the highest mortality rate of all gynecologic. Currently there is no effective screening methodology or accurate early diagnostic test for OC. In recent years, it has been demonstrated that uterine lavage fluid could be useful for OC diagnosis and molecular profiling. Methodology The aim of this study was to screen uterine lavage and ovarian tissue samples form Lithuanian OC patients for cancer-related mutations by targeted next generation sequencing (NGS) and to determine their associations with clinical features. DNA from 35 uterine lavage fluid from ovarian cancer, uterine cancer and benign ovarian mass patients and 20 ovarian tissue samples were analysed using NGS. The sequencing libraries were prepared using Ion AmpliSeq™ On-Demand Panel targeting 10 OC related genes: BRCA1, BRCA2, PIK3CA, PTEN, KRAS, TP53, CTNNB1, PPP2R1A, ARID1A and FBXW7. Variant uncertain significance (VUS) pathogenity predicted with VarSome database. Results Technique of lavage from uterine cavity was successfully performed in all patients. We were able to detect 37 SNP (22 of these known to be pathogenic) in 20/35 uterine lavage samples, of these 19 (10 known pathogenic mutations) matched SNP found in tissue samples. 4/15 VUS predicted to be pathogenic: ARID1A c.5548delG, c.6628C>T, c.3606delG and BRCA1 c.3871delT. We were able to detect 62.5% (10/16) known pathogenic mutations in both matched samples (n = 17). Most mutations found in patients with serous OC and metastases. Conclusion Cell-free DNA samples obtained from uterine lavage could be used for molecular profiling of OC patients. Uterine lavage is a simple procedure which can be performed in a physician’s office-based setting and it holds great potential and significant promise for earlier diagnosis of OC and suggest the future possibility of this approach for screening women for gynecological cancers. Disclosures This study is supported by NCI research fund.