TY - JOUR
T1 - The cutoff for estrogen and progesterone receptor expression in endometrial cancer revisited: a European Network for Individualized Treatment of Endometrial Cancer collaboration study
AU - van Weelden, Willem Jan
AU - Reijnen, Casper
AU - Küsters-Vandevelde, Heidi V. N.
AU - Bulten, Johan
AU - Bult, Peter
AU - Leung, Samuel
AU - Visser, Nicole C. M.
AU - Santacana, Maria
AU - Bronsert, Peter
AU - Hirschfeld, Marc
AU - Colas, Eva
AU - Gil-Moreno, Antonio
AU - Reques, Armando
AU - Mancebo, Gemma
AU - Huvila, Jutta
AU - Koskas, Martin
AU - Weinberger, Vit
AU - Bednarikova, Marketa
AU - Hausnerova, Jitka
AU - Snijders, Marc P. L. M.
AU - Matias-Guiu, Xavier
AU - Amant, Frédéric
AU - Krakstad, Camilla
AU - van de Vijver, Koen
AU - ENITEC-consortium
AU - McAlpine, Jessica
AU - Pijnenborg, Johanna M. A.
N1 - Publisher Copyright: © 2020 Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/3/1
Y1 - 2021/3/1
N2 - 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.
AB - 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.
KW - Cutoff
KW - Endometrial cancer
KW - Estrogen receptor
KW - Progesterone receptor
KW - Prognostic biomarker
UR - http://www.scopus.com/inward/record.url?scp=85099362452&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.humpath.2020.12.003
DO - https://doi.org/10.1016/j.humpath.2020.12.003
M3 - Article
C2 - 33338506
SN - 0046-8177
VL - 109
SP - 80
EP - 91
JO - Human Pathology
JF - Human Pathology
ER -