OBJECTIVE: Pre-operative immunohistochemical (IHC) biomarkers are not incorporated in endometrial cancer (EC) risk classification. We aim to investigate the added prognostic relevance of IHC biomarkers to the ESMO-ESGO-ESTRO risk classification and lymph node (LN) status in EC. METHODS: Retrospective multicenter study within the European Network for Individualized Treatment of Endometrial Cancer (ENITEC), analyzing pre-operative IHC expression of p53, L1 cell-adhesion molecule (L1CAM), estrogen receptor (ER) and progesterone receptor (PR), and relate to ESMO-ESGO-ESTRO risk groups, LN status and outcome. RESULTS: A total of 763 EC patients were included with a median follow-up of 5.5-years. Abnormal IHC expression was present for p53 in 112 (14.7%), L1CAM in 79 (10.4%), ER- in 76 (10.0%), and PR- in 138 (18.1%) patients. Abnormal expression of p53/L1CAM/ER/PR was significantly related with higher risk classification groups, and combined associated with the worst outcome within the 'high and advanced/metastatic' risk group. In multivariate analysis p53-abn, ER/PR- and ESMO-ESGO-ESTRO 'high and advanced/metastatic' were independently associated with reduced disease-specific survival (DSS). Patients with abnormal IHC expression and lymph node metastasis (LNM) had the worst outcome. Patients with LNM and normal IHC expression had comparable outcome with patients without LNM and abnormal IHC expression. CONCLUSION: The use of pre-operative IHC biomarkers has important prognostic relevance in addition to the ESMO-ESGO-ESTRO risk classification and in addition to LN status. For daily clinical practice, p53/L1CAM/ER/PR expression could serve as indicator for surgical staging and refine selective adjuvant treatment by incorporation into the ESMO-ESGO-ESTRO risk classification.

Biomedical Research Group in Gynaecology Vall Hebron Institute of Research Universitat Autònoma de Barcelona CIBERONC Barcelona Spain

Centre for Cancer Biomarkers Department of Clinical Science University of Bergen Bergen Norway; Mohn Medical Imaging and Visualization Centre Department of Radiology Haukeland University Hospital Bergen Norway

Department of Internal Medicine Hematology and Oncology University Hospital in Brno and Masaryk University Brno Czech Republic

Department of Obstetrics and Gynaecology Canisius Wilhelmina Hospital Nijmegen the Netherlands

Department of Obstetrics and Gynaecology Department Bichat Claude Bernard Hospital Paris France

Department of Obstetrics and Gynaecology Haukeland University Hospital Bergen Norway

Department of Obstetrics and Gynaecology Haukeland University Hospital Bergen Norway; Centre for Cancer Biomarkers Department of Clinical Science University of Bergen Bergen Norway

Department of Obstetrics and Gynaecology Hospital del Mar PSMAR Barcelona Spain

Department of Obstetrics and Gynaecology Radboud university medical center Nijmegen the Netherlands

Department of Obstetrics and Gynaecology Radboud university medical center Nijmegen the Netherlands; Department of Obstetrics and Gynaecology Canisius Wilhelmina Hospital Nijmegen the Netherlands

Department of Obstetrics and Gynaecology University Hospital in Brno and Masaryk University Brno Czech Republic

Department of Oncology KU Leuven Leuven Belgium; Department of Gynaecologic Oncology Netherlands Cancer Institute and Amsterdam Medical Centers Amsterdam the Netherlands

Department of Pathology and Molecular Genetics and Research Laboratory Hospital Universitari Arnau de Vilanova University of Lleida IRBLleida CIBERONC Lleida Spain

Department of Pathology Canisius Wilhelmina Hospital Nijmegen the Netherlands

Department of Pathology Elisabeth TweeSteden Hospital Tilburg the Netherlands

Department of Pathology Ghent University Hospital Cancer Research Institute Ghent Ghent Belgium

Department of Pathology Radboud university medical center Nijmegen the Netherlands

Department of Pathology Stichting PAMM Eindhoven the Netherlands; Department of Pathology Radboud university medical center Nijmegen the Netherlands

Department of Pathology University Hospital in Brno and Masaryk University Brno Czech Republic

Department of Pathology University of Turku Turku Finland

Department of Radiation Oncology Radboud university medical center Nijmegen the Netherlands

Gynecological Department Vall Hebron University Hospital CIBERONC Barcelona Spain; Pathology Department Vall Hebron University Hospital CIBERONC Barcelona Spain

Strahlenther Onkol. 2021 Dec;197(12):1148-1150. doi: 10.1007/s00066-021-01862-6. PubMed

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