Comparison of the clinical and genomic profiles of endometrial cancer in Appalachian and non-Appalachian patients.

• DOI: 10.1200/jco.2024.42.16_suppl.5591
• Publication Date: 2024-06-06T20:14:27Z
• Authors: Taylor A Rives; Abu Saleh Mosa Fa...; Jinpeng Liu; Hye Sook Chon; Casey Cosgrove; Bradley Corr; Robert Dood; Stephen B. Edge; Aliza L. Leiser; Christina Washington; Bodour Salhia; Chris Moskaluk; Neil T. Phippen; Lisa Michelle Lan...; Dava West Piecoro; Michelle Churchman; Charles S Dietrich; Frederick R Ueland; Chi Wang; Jill Kolesar
• Keywords: Appalachian Region

5591 Background: Kentucky has the highest incidence and mortality from gynecologic cancer in United States, of endometrial (EC) Appalachian (AP) population is even higher than non-Appalachian (non-AP). The purpose this study to compare demographics, molecular profiles, outcomes between AP non-AP populations. Methods: Using Total Cancer Care prospective cohort study, we evaluated 836 women with EC, 40 (4.8%), 700 (83.7%), 96 unknown residence (11.5%). We used descriptive statistics univariate analyses vs MutSig identify significantly mutated genes. RNASeq data was trimmed processed STAR. Differential expression pathway enrichment were EdgeR GSEA, respectively. grouped patients by POLE mutation first, then microsatellite instability (MSI) high. identified CN clusters hierarchical clustering remainder status. compared overall survival (OS) among subgroups using Kaplan-Meier curves log-rank tests. Results: Most participants white (90.2%), had a median age 62.7 years, BMI 34.0 mg/m 2 , stage I disease (64.6%), endometrioid histology (83.3%). diagnosed at (stage IV 25.8% 7.7%, p=0.0008) more likely have serous carcinoma (33.3% 9.0%, p<0.0001). There no difference age, race, or non-AP. group EVI5 mutations (17.5% 6.0%, p=0.012), as well significant differences RNA expression, specifically upregulation oxidative phosphorylation pathways. Cluster (c) analysis 6 clusters; c corresponded TCGA high group, divided low into two distinct subgroups: moderate (c 1,3,4,6) 5) there alteration these clusters. worse OS, improved intermediate OS (p<0.0001); significance persisted when controlling for covariates. (n=245, 29.52%), followed MSI High (n=210, 25.3%), (n=175, 21.1%), (n=160, 19.3%), POLEmutated (n=40, 4.8%). Conclusions: This larger independent replicate subtyping, which includes previously unevaluated population. additional new different survival. advanced disease, histology, mutations, an oncogene involved cell cycle regulation not implicated EC. also expression. These may reveal opportunities treatment reduce disparities.