CHAPTER 6 138 three-tiered ER/PR classification within the molecular subgroups in EC. It is hypothesized that this three-tiered model refines prognostication within all molecular subgroups. MATERIALS AND METHODS A retrospective multicenter cohort study has been performed. Data was used from the European Network for Individualized Treatment (ENITEC) centers and Vancouver, Canada. Data from four previously published and one unpublished cohort were collected, resulting in 978 patients (flowchart Supplementary Figure S1).10, 12, 13, 18, 19 Patients were treated between 1994-2019 (median 2007) and data on clinicopathological characteristics and outcome were collected. Inclusion criteria were: (I) availability of ER/PR immunohistochemistry, (II) patients successfully classified with either full next-generation sequencing (NGS) or NGS combined with IHC according to ProMisE12. An exclusion criteria was: missing follow-up. Patients were aligned according to the diagnostic algorithm in Figure 1 and final classified according to the World Health organization (WHO) classification of Female Genital tumors20; POLEmut, MMRd, p53mut and NSMP. This study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline. Figure 1. Diagnostic algorithm of patients diagnosed with full next-generation sequencing or combined with immunohistochemistry, and the final classification according to the World Health organization (WHO) classification of female genital tumors. Abbreviations: POLE, Polymerase epsilon; MSI, Microsatellite instability; MMRd, Mismatch repair deficient; TP53, Tumor protein 53; p53mut, p53-mutant; NSMP, No-specific molecular profile
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