mice were randomized into treatment arms including vehicle control, CGX-1321, paclitaxel, and combination of CGX-1321 and paclitaxel. Mice receiving CGX-1321 (1 mg/kg) or vehicle received appropriate formulation once daily by oral gavage. Paclitaxel was given via intraperitoneal injection (5 mg/kg, 3 days on, 3 days off). After 14 days of treatment, mice were sacrificed, and omentums were harvested for analysis by flow cytometry. Tissue was processed for flow cytometric analysis of Tregs, CD8 + and CD4 + T-cells, and dendritic cells, and immune checkpoint markers PD-1, CTLA-4, and FOXP3. Statistical analysis was done in GraphPad Prism. Results: Administration of CGX-1321 alone inhibited tumor growth, as evidenced by omentum weight, while reducing expression of PD- 1, although not significantly, and paradoxically increasing CTLA-4 expression. There was a trend toward an increase in Tregs, and in CD103 + dendritic cells, but a slight decrease in CD8 + cells; however, these effects did not reach significance. Paclitaxel alone also reduced tumor burden and had similar effects on T cells and immune markers, except for a decrease in CD103 + dendritic cells. Combining CGX-1321 with paclitaxel further reduced tumor growth and prolonged survival but had no additional effect on the T cell profile. Conclusion: This study indicates that inhibition of the Wnt/β- catenin pathway using CGX-1321 combined with administration of paclitaxel significantly reduced tumor burden in a syngeneic mouse model. Further investigation is required to fully understand any potential effect on T cell function. doi:10.1016/j.ygyno.2019.04.172 1242 - Poster Session Hormonal receptor expression and clinical outcome in ovarian high-grade serous carcinoma S. George a , R. Sowamber b , L. Dodds a , S.E. Jordan a , I. Paudel a , M. Huang a , A. Pinto a , M.P. Schlumbrecht a , P. Shaw b , B.M. Slomovitz a,c . a University of Miami Sylvester Comprehensive Cancer Center, Miami, FL, USA, b Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada, c University of Miami Miller School of Medicine, Miami, FL, USA Objective: Ovarian high-grade serous carcinoma (HGSC) is genet- ically unstable and rapidly growing and diagnosed at advanced stages. Immunohistochemical profiles have demonstrated differ- ential expression of estrogen receptor alpha (ER) and progester- one receptor (PR) in HGSC. Our objective was to investigate the ER and PR in HGSC and its precursor lesions and to assess the influence of ER/PR subtype on OS and ER/PR-driven pathogenesis in HGSC. Method: Data were derived from a cohort of archival HGSC tissue with advanced-stage and adjuvant platinum-based chemotherapy (n = 386) and a cohort of serous tubal intraepithelial carcinoma (STIC, n = 14). Gene set enrichment analyses (GSEA) was performed using mRNA gene expression profiles based on ER/PR expression in tumors (Affymetrix U133, n = 45). Log rank (Mantel-Cox) analysis was used to calculate OS and PFS. Results: ER is maintained in serous tubal intraepithelial lesions (STIC) while PR is lost; 71% of HGSC are ER+ and 29% ER-. ER expression alone was not associated with a significant OS (P = 0.406) and PFS (P = 0.473) advantage, while PR+ displayed significant OS advantages at both the 5% cutoff (60.1 months, 95% CI 49.1–71.3, vs 44 months, 95% CI 37.6–52.1, P = 0.008) and the 10% cutoff (60.3 months, 95% CI 48.5– 72.2 vs 47.8 months, 95% CI 40.3–55.2, P = 0.019). Clinical outcome assessment on ER/PR status showed ER+/PR- (5% cutoff expression, 51% of cohort) patients had significantly lower OS (41.7 months, 95% CI 35.0–48.4) relative to ER-/PR+ (63.1 months, 95% CI 35.6–90.6, P = 0.041). GSEA analyses demonstrated upregulation of meiotic recombi- nation (P = 0.00, NES = 2.15), RNA polymerase I transcription (P = 0.00, NES = 2.14), double strand break repair (P = 0.00, NES = 1.86), and Fanconi pathways (P = 0.00, NES = 1.84) in ER-/PR+ tumors. Upregulation of interferon alpha, beta (P = 0.0, NES = 2.12) gamma signaling (P = 0.0018, NES = 1.77) and antigen presentation pathways (P = 0.0, NES = 2.12) was identified in the worse survival group, ER+/ PR–. Conclusion: Hormone receptor status in HGSC is heterogeneous. PR receptor loss occurs during tumor evolution between normal FTE and STIC. Progesterone receptor expression confers improved OS driven by an increase in mitotic activity and suppression in interferon beta and gamma signaling. doi:10.1016/j.ygyno.2019.04.173 1243 - Poster Session Context-dependent environmental influences on endometrial cancer histotype and genotype K.C. Kurnit, L.J. Washburn, R. Broaddus. The University of Texas MD Anderson Cancer Center, Houston, TX, USA Objective: MLH1 gene methylation is the main cause for sporadic microsatellite instability-high (MSI-H) endometrial cancer and is one of the most common molecular changes seen in endometrial cancer. It is well established that environmental influences such as nutritional state can have an impact on gene methylation. We hypothesized that environmental factors were associated with MLH1-methylated endo- metrial cancers. Method: A cohort of patients with sporadic microsatellite-stable (MSS) and MLH1-methylated MSI-H sporadic endometrial tumors was retrospectively identified following the usual clinical evalua- tion for Lynch syndrome. Patients with suspected Lynch syndrome based on this initial screening were excluded. Clinical and pathology characteristics were identified by review of the medical record and were compared across groups using comparative statistics. Results: A total of 463 patients were included; 349 (75%) of tumors were MSS, and 114 (25%) were sporadic MLH1-methylated, MSI- high. Patients with MLH1-metylated tumors were significantly older than those with MSS tumors (65 vs 58 years, P b 0.001). MLH1- methylated tumors were more often grade 3 (14% vs 5%, P b 0.001) and more often had lymphatic/vascular space invasion (LVSI) (42% vs 27%, P = 0.003). There were no differences in race, BMI, histology, or myometrial invasion across groups. Further analyses of environ- mental factors were performed after stratifying endometrioid tumors into low (grades 1–2) and high grade (grade 3). Patients with low–grade, MLH1-methylated, MSI-high tumors were significantly older at diagnosis (65 vs 57 years, P b 0.001), but had no difference in mean BMI. Alternatively, patients with high-grade, MLH1-methylated, MSI-high tumors had significantly higher BMIs (36 vs 28 kg/m 2 , P = 0.02), but no difference in mean age. See Table 1. Conclusion: The relationship of endometrioid grade with environ- mental characteristics is complex. While causality cannot be certain, these data suggest that the environmental impact of obesity may promote MLH1 methylation, which may be linked with increased prevalence of grade 3 disease and LVSI. A provocative hypothesis moving forward is that weight loss could induce a “molecular switch” to alter the histologic and molecular characteristics of an endometrial tumor. 0090-8258/$ – see front matter Abstracts / Gynecologic Oncology 154 (2019) 2–288 73