AMOUNT OF PREOPERATIVE ENDOMETRIAL TISSUE 31 2 independently by two investigators (AH, CR) to assess the degree of inter-rater variability and intraclass correlation coefficient (ICC). A set of 90 slides were double-checked by a third investigator (SV) to ensure ImageJ selected the proper tissue. Statistical analysis All statistical analyses were performed using IBM Statistical Package for the Social Sciences (SPSS) statistics for Windows, version 25.0 (released 2017, Armonk, NY, United States) and P<0.05 was considered statistically significant. For observing within the low- and highgrade classification, the pre- and postoperative tumor diagnosis was specified in individual FIGO tumor grade and histological subtype. These included the original diagnosis (including premalignant tissue); grade 1, grade 2, grade 3 EEC or NEEC. For continuous data that were not normally distributed, the Mann-Whitney U and Kruskal Wallis test were used to compare the differences in median endometrial tissue surface and patient characteristics. Clinicopathological characteristics between dichotomous subgroups were compared using the χ2 or Fisher’s exact test for categorical data. Survival analyses were performed using the Kaplan Meier curves (first 10 years after diagnosis). Disease-specific survival (DSS) was defined as time from date of diagnosis to date of death from EC, all censored by date of last contact. RESULTS Patients From the original cohort of 1199 patients, 644 preoperative biopsies were available, of those 46 patients were excluded because absence of tumor tissue due to insufficient amount of tissue and benign endometrium and 25 because of an unspecified grade on preoperative biopsy, resulting in a total of 573 patients included in this study with a median follow-up of 5.7 years (Supplementary Figure S2). Excluded patients did not significantly differ from included patients with respect to tumor histology (data not shown). Baseline characteristics for all included patients, classified into postoperative low- and high-grade EC, are summarized in Table 1. Among these 573 patients, 462 patients (80.6%) were postoperative low-grade and 111 (19.4%) high-grade EC. The mean age at diagnosis was 64.8 years, most patients were preoperative diagnosed with grade 1 EEC (53.8%) and postoperative FIGO stage I (82.9%). The most used preoperative sampling method was the pipelle (45.2% ). Patients diagnosed with postoperative high-grade EC were significantly older, had lower Body Mass Index (BMI), more often LNM, subsequently resulting in more applied adjuvant chemotherapy and chemoradiotherapy compared to patients with low-grade EC.
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