The cut-off for estrogen and progesterone receptor in endometrial cancer revisited: an ENITEC collaboration study

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.