CHAPTER 5 120 S4 C). Patients with LNM (N1) and ER/PR- had significantly reduced DSS compared with patients having LNM (N1) and ER/PR+ (Supplementary Figure S5 C). Patients without LNM (N0) and abnormal IHC expression (p53-abn, L1CAM+ or ER/PR-) had similar RFS/DSS compared with patients with LNM (N1) and normal IHC expression (p53-wt, L1CAM- or ER/PR+) (Supplementary Figure S4 A-C and S5 A-C). DISCUSSION In this study the added prognostic relevance of the pre-operative IHC expression of p53, L1CAM and ER/PR, to the ESMO-ESGO-ESTRO risk classification groups is demonstrated. Significantly increased abnormal IHC expression is observed in higher risk classification groups. Within the ‘high and advanced/metastatic’ risk group, patients with a combination of abnormal IHC expression had the poorest outcome (RFS and DSS). ER/PR-, p53-abn, and ESMO-ESGO-ESTRO ‘high and advanced/metastatic’ risk group were independently associated with decreased DSS. Furthermore, abnormal IHC expression had added prognostic relevance to LN status. Patients with abnormal IHC expression and LNM had most dismal outcome. Interestingly, patients without LNM and abnormal IHC expression showed comparable RFS/DSS as, patients with LNM and normal biomarkers. This indicated that the IHC biomarkers p53, L1CAM and ER/PR have prognostic relevance to the ESMO-ESGOESTRO risk classification groups and to patients with and without LNM. Our findings of p53-abn as important prognosticator is in line with the TCGA data that have been validated by multiple other research groups10, 21. The percentage of p53-abn in our study cohort (12.0%) in patients with endometroid histology was comparable to the original TCGA paper (11.4%)10. Instead of using p53 sequencing, we used easy accessible p53 IHC staining comparable to the ProMisE classification system, which was shown to be a good surrogate biomarker for p53 mutations11, 13, 22. Talhouk et al. studied the prevalence and prognostic relevance of p53-abn in the ESMO risk classification, and observed a high prevalence of p53-abn in the ESMO ‘high’ risk group in line with our findings13. The fact that integration of ProMisE/TCGA in the ESMO risk classification did not show significant difference in outcome, is contrary to our results in which p53-abn had added prognostic value in the ‘high and advanced/metastatic’ risk group. This could be explained by the use of the ESMO 2013 guideline in the study of Talhouk et al. compared with the ESMO-ESGO-ESTRO 2016 guideline used in our study13. In addition to p53-abn, L1CAM+ is an established prognosticator in EC as observed in our study16, 20, 23. The percentage of L1CAM+ cases was slightly lower in our study compared with other studies16, 19, 20, 23, 24. This might be related to the fact that preoperative analysis was
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