CHAPTER 9 204 (n=22 pure CCC and n=21 mixed type CCC), molecular classification was determined by NGS. In addition, IHC staining for the hormone receptors, L1 cell adhesion molecule (L1CAM) and the mismatch repair deficiency (MMRd) proteins (MSH6 and PMS2) were performed. Patients with pure CCC had significantly more frequent TP53 mutations whereas patients with mixed type had more frequent MSI/MMRd and high progesterone receptor expression (>10%). In addition, patients with pure CCC had a significantly worse prognosis than the mixed CCC. In multivariable analysis TP53 mutation was a significant predictor for reduced disease-specific survival, whereas histology (pure and mixed CCC) was not significant. The ESMO-ESGO-ESTRO 2016 (European Society for Medical Oncology - European Society of Gynecological Oncology - European SocieTy for Radiotherapy & Oncology) risk classification groups aim to identify patients for tailoring adjuvant therapy. IHC biomarkers with proven prognostic relevance within EC were not included in these risk groups. In Chapter 5, we investigated whether preoperative IHC biomarkers were prognostically relevant in addition to lymph node status and within the ESMO-ESGO-ESTRO 2016 risk groups in a retrospective ENITEC cohort study (n=763). Patients with positive lymph node status and abnormal expression of IHC showed significantly reduced recurrence-free survival (p53-abnormal, L1CAM+) and significantly reduced disease-specific survival (p53-abnormal, L1CAM+, estrogen and progesterone receptor -). In the ‘high and advanced/metastatic’ risk group, patients with abnormal IHC expression had a significantly lower recurrence-free survival compared with normal IHC expression. Within the multivariate analyses, abnormal expression of p53, <10% expression of the hormonal biomarkers, and the ESMO-ESGOESTRO risk group ‘high and advanced/metastatic’ were independent prognostic factors for the disease-specific survival. Thus, in addition to lymph node status and within the ESMOESGO-ESTRO 2016 risk groups, the biomarkers remained prognostically relevant. In Chapter 6, the role of hormonal biomarkers within molecular classification was investigated in a retrospective study within the ENITEC cohort and a study cohort of Vancouver (Canada). Molecular subgroups were determined using NGS or a combination of NGS and IHC. The expression of hormonal biomarkers was divided into three risk groups: estrogen + progesterone receptor (ER+PR) expression 0-10%, 20-80% and 90-100%, and ‘discordant’ when ER/PR expression were not in the same risk group. A total of 739 patients were included, POLE mutation present in 9.1%, MMRd in 27.6%, p53 mutation in 20.8% and NSMP in 42.5%. In the complete cohort, patients with hormonal expression of 0-10% had significantly the worst 5-year disease-specific survival, 20-80% an intermediate and 90-100% the best. Within the p53 mutation, MSI and NSMP subgroup, the 5-year diseasespecific survival of the different hormonal risk groups was significantly different. Within the multivariate analysis, hormone receptor expression 0-10%, p53 mutation, lymph-vascular
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