Proteomic, Genomic, and Longitudinal Pathways to Ovarian Cancer Biomarker Discovery

This administrative supplement seeks support for administration of the Uterine Lavage Study by the principal investigator and a research coordinator. Since the study has become a multi-year study due to COVID and other reasons, and administrative support was only available for the first year, support is needed to maintain administration of the study in a cohesive and organized fashion. The Uterine Lavage Study (ULS) aims to elucidate the relative contributions to detection of ovarian cancer from tumor DNA in uterine lavage (UL) and in Pap smears, and protein biomarkers from blood, uterine lavage, and Pap smear fluid, using newly available detection and sample collection technologies. Six sites will enroll patients into this study into two cohorts. In the first cohort, the study will enroll 200 patients scheduled for surgery for suspected ovarian cancer. Enrolling patients prior to surgical diagnosis ensures the study will be PRoBE compliant. Up to two blood draws will be obtained preoperatively or up to 31 days prior to surgery, and a uterine lavage and Pap smear will be obtained immediately prior to surgery. The expectation is that ~50 of these patients will have pathologically confirmed ovarian cancer. In a second cohort, 50 patients with an inherited BRCA1 or BRCA2 deleterious mutation without suspected ovarian cancers who are scheduled for risk-reducing salpingooophorectomy (RRSO) will be enrolled. Based on published reports, it is expected that that ~5 patients will have microscopic or low volume ovarian cancer identified on SEE-FIM pathologic examination. In each cohort, the patients with a pathologic invasive epithelial ovarian cancer diagnosis will be defined as Cases and patients without any ovarian cancer, primary peritoneal cancer (PPC), or other cancer identified due to the surgery, will be defined as Controls. Other cancer groups are: (i) PPC, (ii) noninvasive serous tubal intraepithelial carcinoma (STIC) lesions, (iii) non-epithelial ovarian cancers, and (iv) non-ovarian cancers. Analytic sites will determine TP53 mutation status and 25-gene panel mutation status, targeted methylation, global methylation, and protein abundances in the uterine lavage, Pap smear biospecimens, and in blood for cases and controls. Statistical analyses will identify biomarkers which distinguish cases from controls with a high specificity, and determine the complementarity of biomarkers from each biospecimen. Such analyses will identify a classifier based on a panel of biomarkers that is likely to serve as high probability candidates for the early detection of ovarian cancer.