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

Van Weelden, Willem Jan; Reijnen, Casper; Küsters-Vandevelde, Heidi V. N; Bulten, Johan; Bult, Peter; Leung, Samuel; Visser, N. C. M.; Santacana Espasa, Maria; Bronsert, Peter; Hirschfeld, Marc; Colás, Eva; Gil-Moreno, Antonio; Reques, Armando; Mancebo, Gemma; Huvila, Jutta; Koskas, Martin; Weinberger, Vit; Bednarikova, M.; Hausnerova, Jitka; Snijders, Marc P. L. M.; Matias-Guiu, Xavier; Amant, Frederic

doi:https://doi.org/10.1016/j.humpath.2020.12.003

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2021

Author

Van Weelden, Willem Jan

Reijnen, Casper

Küsters-Vandevelde, Heidi V. N

Bulten, Johan

Bult, Peter

Leung, Samuel

Visser, N. C. M.

Santacana Espasa, Maria

Bronsert, Peter

Hirschfeld, Marc

Colás, Eva

Gil-Moreno, Antonio

Reques, Armando

Mancebo, Gemma

Huvila, Jutta

Koskas, Martin

Weinberger, Vit

Bednarikova, M.

Hausnerova, Jitka

Snijders, Marc P. L. M.

Matias-Guiu, Xavier

Amant, Frederic

Suggested citation

Van Weelden, Willem Jan; Reijnen, Casper; Küsters-Vandevelde, Heidi V. N; Bulten, Johan; Bult, Peter; Leung, Samuel; ... Amant, Frederic. (2021) . The cutoff for estrogen and progesterone receptor expression in endometrial cancer revisited: a European Network for Individualized Treatment of Endometrial Cancer collaboration study. Human Pathology, 2021, vol. 109, p. 80-91. https://doi.org/10.1016/j.humpath.2020.12.003.

Abstract

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.