Stephanie Vrede

CHAPTER 6 140 Statistical analysis The molecular subgroups were compared with the dichotomous clinicopathological characteristics using the χ2 or Fisher’s exact test for categorical data, and the non-parametric Mann-Whitney U-test for continuous variables. Survival analyses were performed using Kaplan-Meier curves and univariable and multivariable Cox-regression analysis. Associations are shown as hazard ratio (HR), 95% CI and P-value. The including covariates in multivariable analysis are the main known prognostic biomarkers in EC. Myometrial invasion (MI) was excluded because this is already included in FIGO stage and grade was excluded because this is represented by ER/PR expression. Disease-specific survival (DSS) was defined as time from date of diagnosis to date of death by EC all censored by date of last contact. The results were considered significant with P-value less than 0.05. Statistical Package for the Social Sciences, version 27.0 (IBM, New York, NY, USA) was used for statistical analyses. RESULTS In total, 978 patients with known and classifiable ER/PR IHC status were available for molecular analysis. Only patients with a successful molecular analysis were included, resulting in 747 EC patients. In which 8 patients were excluded due to missing follow-up, leading to a total of 739 patients included in this study (Flowchart Supplementary Figure S1). A baseline overview of each included cohort is shown in Supplementary Table 1. The baseline characteristics of the entire cohort are shown in Table 1. Median age was 65.0 (31.0-93.0) years, median BMI 29.0 (15.8-66.2) kg/m2 and median follow-up 60.0 (1.0-283.0) months. The majority of the patients revealed EEC histology 80.4% (N=594), grade 1-2 EEC 53.5% (N=394) and FIGO stage I-II 75.5% (N=558). A minority of patients was diagnosed with ER+PR expression 0-10% or 90-100% (respectively, 16.8% (N=124) and 17.1% (N=126)). A total of 251 patients (34.0%) was not aligned to one of the three risk groups and classified as ‘discordant’. Most discordant cases are located in patients with ER 20-80% + PR 0-10% expression (13.4%), and PR 20-80% + ER 90-100% expression (12.3%) (data not shown). Tumors were classified as POLEmut in 9.1% (N =67), MMRd in 27.6% (N =204), p53mut in 20.8% (N =154), and NSMP in 42.5% (N =314), in line with the original TCGA paper11. The majority of patients within the POLEmut, MMRd and NSMP subgroups had EEC histology (respectively, 88.1%, 91.7%, 92.7%), whereas the majority of patients within the p53mut subgroup had NEEC histology (63.0%).

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