Willem Jan van Weelden1, Casper Reijnen2, Heidi V N Küsters-Vandevelde3, Johan Bulten4, Peter Bult4, Samuel Leung5, Nicole C M Visser6, Maria Santacana7, Peter Bronsert8, Marc Hirschfeld9, Eva Colas10, Antonio Gil-Moreno11, Armando Reques12, Gemma Mancebo13, Jutta Huvila14, Martin Koskas15, Vit Weinberger16, Marketa Bednarikova17, Jitka Hausnerova18, Marc P L M Snijders19, Xavier Matias-Guiu7, Frédéric Amant20, Camilla Krakstad21, Koen van de Vijver22, Jessica McAlpine23, Johanna Pijnenborg24. 1. Department of Obstetrics and Gynaecology, Radboud university medical center, Nijmegen, the Netherlands. Electronic address: willemjan.vanweelden@radboudumc.nl. 2. Department of Obstetrics and Gynaecology, Radboud university medical center, Nijmegen, the Netherlands; Department of Obstetrics and Gynaecology, Canisius-Wilhelmina Hospital, Nijmegen, the Netherlands. 3. Department of Pathology, Canisius-Wilhelmina Hospital, Nijmegen, The Netherlands. 4. Department of Pathology, Radboud university medical center, Nijmegen, the Netherlands. 5. Genetic Pathology Evaluation Center, Vancouver General Hospital, Vancouver, British Columbia, Canada. 6. Foundation Laboratory for Pathology and Medical Microbiology (PAMM), Eindhoven, The Netherlands. 7. Department of Pathology and Molecular Genetics and Research Laboratory, Hospital Universitari Arnau de Vilanova, University of Lleida, IRBLleida, CIBERONC, Lleida, Spain. 8. Institute of Pathology, University Medical Center, Freiburg, Germany. 9. Department of Obstetrics and Gynecology, University Medical Center, Freiburg; German Cancer Consortium, German Cancer Research Center, Heidelberg, Germany; Institute of Veterinary Medicine, Georg-August-University, Goettingen, Germany. 10. Biomedical Research Group in Gynecology, Vall Hebron Institute of Research, Universitat Autònoma de Barcelona, CIBERONC, Barcelona, Spain. 11. Biomedical Research Group in Gynecology, Vall Hebron Institute of Research, Universitat Autònoma de Barcelona, CIBERONC, Barcelona, Spain; Gynecological Department, Vall Hebron University Hospital, CIBERONC, Barcelona, Spain. 12. Pathology Department, Vall Hebron University Hospital, CIBERONC, Barcelona, Spain. 13. Department of Obstetrics and Gynecology, Hospital del Mar, PSMAR, Barcelona, Spain. 14. Department of Pathology, University of Turku, Turku, Finland. 15. Obstetrics and Gynecology Department, Bichat-Claude Bernard Hospital, Paris, France. 16. Department of Gynecology and Obstetrics, Faculty of Medicine, Masaryk University, Brno, Czech Republic. 17. Department of Internal medicine, oncology and hematology, Faculty of Medicine, Masaryk University, Brno, Czech Republic. 18. Institute of Pathology, Faculty of Medicine, Masaryk University, Brno, Czech Republic. 19. Department of Obstetrics and Gynaecology, Canisius-Wilhelmina Hospital, Nijmegen, the Netherlands. 20. Department of Oncology, KU Leuven, Leuven, Belgium; Center for Gynaecologic Oncology, Netherlands Cancer Institute and Amsterdam University Medical Center, Amsterdam, the Netherlands. 21. Department of Obstetrics and Gynecology, Haukeland University Hospital, Bergen, Norway; Centre for Cancer Biomarkers, Department of Clinical Science, University of Bergen, Bergen, Norway. 22. Department of Pathology, Ghent University Hospital, Cancer Research Institute Ghent (CRIG), Ghent, Belgium; Department of Pathology, University Hospital Antwerp, Antwerp, Belgium. 23. Obstetrics and Gynecology, University of British Columbia, Vancouver, British Columbia, Canada. 24. Department of Obstetrics and Gynaecology, Radboud university medical center, Nijmegen, the Netherlands.
Abstract
BACKGROUND: there is no consensus on the cut-off for positivity of estrogen receptor (ER) and progesterone receptor (PR) in endometrial cancer (EC). Therefore we determined the cut-off value for ER and PR with the strongest prognostic impact on outcome. METHODS: immunohistochemical expression of ER and PR was scored as a percentage of positive EC cell nuclei. Cut-off values were related to disease-specific (DSS) and disease-free survival (DFS) using sensitivity, specificity and multivariable regression analysis. The results were validated in an independent cohort. RESULTS: the study cohort (n=527) included 82% grade 1-2 and 18% grade 3 ECs. Specificity for DSS and DFS was highest for the cut-off values 1-30%. Sensitivity was highest for the cut-offs 80-90%. ER and PR expression were independent markers for DSS at cut-off values of 10% and 80%. Consequently, three subgroups with distinct clinical outcome were identified: ER/PR 0-10%: unfavorable outcome (5-year-DSS 75.9-83.3%); ER/PR 20-80%: intermediate outcome (5-year-DSS 93.0-93.9%) and ER/PR 90-100%: favorable outcome (5-year-DSS 97.8-100%). The association between ER/PR subgroups and outcome was confirmed in the validation cohort (n=265). CONCLUSIONS: we propose classification of ER and PR expression according to a high risk (0-10%), intermediate risk (20-80%) and low risk (90-100%) group.
BACKGROUND: there is no consensus on the cut-off for positivity of estrogen receptor (ER) and progesterone receptor (PR) in endometrial cancer (EC). Therefore we determined the cut-off value for ER and PR with the strongest prognostic impact on outcome. METHODS: immunohistochemical expression of ER and PR was scored as a percentage of positive EC cell nuclei. Cut-off values were related to disease-specific (DSS) and disease-free survival (DFS) using sensitivity, specificity and multivariable regression analysis. The results were validated in an independent cohort. RESULTS: the study cohort (n=527) included 82% grade 1-2 and 18% grade 3 ECs. Specificity for DSS and DFS was highest for the cut-off values 1-30%. Sensitivity was highest for the cut-offs 80-90%. ER and PR expression were independent markers for DSS at cut-off values of 10% and 80%. Consequently, three subgroups with distinct clinical outcome were identified: ER/PR 0-10%: unfavorable outcome (5-year-DSS 75.9-83.3%); ER/PR 20-80%: intermediate outcome (5-year-DSS 93.0-93.9%) and ER/PR 90-100%: favorable outcome (5-year-DSS 97.8-100%). The association between ER/PR subgroups and outcome was confirmed in the validation cohort (n=265). CONCLUSIONS: we propose classification of ER and PR expression according to a high risk (0-10%), intermediate risk (20-80%) and low risk (90-100%) group.
Authors: Heidi Rütten; Cornelia Verhoef; Willem Jan van Weelden; Anke Smits; Joëlle Dhanis; Nelleke Ottevanger; Johanna M A Pijnenborg Journal: Cancers (Basel) Date: 2021-12-14 Impact factor: 6.639