The cutoff for estrogen and progesterone receptor expression in endometrial cancer revisited: a European Network for Individualized Treatment of Endometrial Cancer collaboration study

Authors	WEELDEN Willem Janvan REIJNEN Casper KÜSTERS-VANDEVELDE Heidi V.N. BULTEN Johan BULT Peter LEUNG Samuel VISSER Nicole C.M. SANTACANA Maria BRONSERT Peter HIRSCHFELD Marc COLAS Eva GIL-MORENO Antonio REQUES Armando MANCEBO Gemma HUVILA Jutta KOSKAS Martin WEINBERGER Vít BEDNAŘÍKOVÁ Markéta HAUSNEROVÁ Jitka SNIJDERS Marc P.L.M. MATIAS-GUIU Xavier AMANT Frédéric
Year of publication	2021
Type	Article in Periodical
Magazine / Source	Human Pathology
MU Faculty or unit	Faculty of Medicine
Citation
Web	https://www.sciencedirect.com/science/article/pii/S0046817720302550?via%3Dihub
Doi	http://dx.doi.org/10.1016/j.humpath.2020.12.003
Keywords	Endometrial cancer; Estrogen receptor; Progesterone receptor; Cutoff; Prognostic biomarker
Description	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.