There is no consensus on the cutoff for positivity of estrogen receptor (ER) and progesterone receptor (PR) in endometrial cancer (EC). Therefore, we determined the cutoff value for ER and PR expression with the strongest prognostic impact on the outcome. Immunohistochemical expression of ER and PR was scored as a percentage of positive EC cell nuclei. Cutoff values were related to disease-specific survival (DSS) and disease-free survival (DFS) using sensitivity, specificity, and multivariable regression analysis. The results were validated in an independent cohort. The study cohort (n = 527) included 82% of grade 1-2 and 18% of grade 3 EC. Specificity for DSS and DFS was highest for the cutoff values of 1-30%. Sensitivity was highest for the cutoff values of 80-90%. ER and PR expression were independent markers for DSS at cutoff values of 10% and 80%. Consequently, three subgroups with distinct clinical outcomes were identified: 0-10% of ER/PR expression with, unfavorable outcome (5-year DSS = 75.9-83.3%); 20-80% of ER/PR expression with, intermediate outcome (5-year DSS = 93.0-93.9%); and 90-100% of ER/PR expression with, favorable outcome (5-year DSS = 97.8-100%). The association between ER/PR subgroups and outcomes was confirmed in the validation cohort (n = 265). We propose classification of ER and PR expression based on a high-risk (0-10%), intermediate-risk (20-80%), and low-risk (90-100%) group.

Biomedical Research Group in Gynecology Vall Hebron Institute of Research Universitat Autònoma de Barcelona CIBERONC 08035 Barcelona Spain

Biomedical Research Group in Gynecology Vall Hebron Institute of Research Universitat Autònoma de Barcelona CIBERONC 08035 Barcelona Spain; Gynecological Department Vall Hebron University Hospital CIBERONC 08035 Barcelona Spain

Department of Gynecology and Obstetrics Faculty of Medicine Masaryk University 62500 Brno Czech Republic

Department of Internal Medicine Oncology and Hematology Faculty of Medicine Masaryk University 62500 Brno Czech Republic

Department of Obstetrics and Gynaecology Canisius Wilhelmina Hospital Nijmegen 6532 SZ the Netherlands

Department of Obstetrics and Gynaecology Radboud University Medical Center 6525 GA Nijmegen the Netherlands

Department of Obstetrics and Gynaecology Radboud University Medical Center 6525 GA Nijmegen the Netherlands; Department of Obstetrics and Gynaecology Canisius Wilhelmina Hospital Nijmegen 6532 SZ the Netherlands

Department of Obstetrics and Gynecology Hospital del Mar PSMAR 08003 Barcelona Spain

Department of Obstetrics and Gynecology University Medical Center 79106 Freiburg Germany; Institute of Veterinary Medicine Georg August University 37073 Goettingen Germany

Department of Oncology KU Leuven 3000 Leuven Belgium; Center for Gynaecologic Oncology Netherlands Cancer Institute and Amsterdam University Medical Center 1066 CX Amsterdam the Netherlands

Department of Pathology and Molecular Genetics and Research Laboratory Hospital Universitari Arnau de Vilanova University of Lleida IRBLleida CIBERONC 25198 Lleida Spain

Department of Pathology Canisius Wilhelmina Hospital Nijmegen 6532 SZ the Netherlands

Department of Pathology Radboud University Medical Center Nijmegen 6525 GA the Netherlands

Department of Pathology University of Turku 20500 Turku Finland

Foundation Laboratory for Pathology and Medical Microbiology 5623 EJ Eindhoven the Netherlands

Genetic Pathology Evaluation Center Vancouver General Hospital Vancouver BC V5Z 1M9 British Columbia Canada

Institute of Pathology Faculty of Medicine Masaryk University 62500 Brno Czech Republic

Institute of Pathology University Medical Center 79106 Freiburg Germany

Obstetrics and Gynecology Department Bichat Claude Bernard Hospital 75018 Paris France

Pathology Department Vall Hebron University Hospital CIBERONC 08035 Barcelona Spain

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