CHAPTER 3 52 INTRODUCTION More than 85% of endometrial cancer (EC) patients present with low-grade histology (grade 1-2) FIGO (International Federation of Gynecology and Obstetrics) early-stage (I-II) endometrioid EC (EEC), and have a favorable prognosis with a 5-year overall survival of 95%.1, 2 Standard treatment consists of hysterectomy with bilateral salpingo-oophorectomy, including lymph node staging for patients with substantial risk of lymph node metastasis.2 The Cancer Genome Atlas (TCGA) defined four important prognostic molecular subgroups in EC based on integrated genomic data: I) ultramutated tumors with polymerase epsilon (POLE) mutations, II) microsatellite instability (MSI), III) copy-number-high (CNH) with frequent tumor protein (TP53) mutations, IV) copy-number-low (CNL) (also known as nospecific molecular profile (NSMP)). These subgroups increase insight in biological tumor behavior based on molecular signature beyond current morphological classification.3 Patients with TP53-mutant tumors have the worst outcome, representing 15% of all EC diagnosis and responsible for 50-70% of all EC-related mortality.4, 5 For decades, tumor grading and FIGO staging have been used to guide primary and adjuvant treatment.6 Currently, with incorporation of the molecular classification to guide adjuvant treatment, the prognostic relevance of tumor grading has gained less attention.7 Molecular profiling has shown to improve prognostication mainly in patients with high-grade EC, probably due to poor interobserver reproducibility of morphological classification and the prognostic and intratumoral heterogeneity of high-grade ECs.5, 8 So far, no data has been reported about the prognostic relevance of molecular profiling specifically in patients with low-grade EC. The aim of this study is to determine the prognostic relevance of molecular profiling within low-grade EC. As most patients present with low-grade EC and have an excellent outcome, we hypothesized that molecular profiling might be less useful in these patients. MATERIALS AND METHODS Data source This retrospective European multicenter study consisted of data out of four previously published studies and one submitted, all published by our research group.9-13 A baseline overview and flowchart of the included studies is shown in eTable 1 and eFigure 1 in the supplement. This study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline.
RkJQdWJsaXNoZXIy MTk4NDMw