TY - JOUR
T1 - Hormonal biomarkers remain prognostically relevant within the molecular subgroups in endometrial cancer
AU - Vrede, Stephanie W.
AU - Van Weelden, Willem Jan
AU - Bulten, Johan
AU - Gilks, C. Blake
AU - Teerenstra, Steven
AU - Huvila, Jutta
AU - Matias-Guiu, Xavier
AU - Gil-Moreno, Antonio
AU - Asberger, Jasmin
AU - Sweegers, Sanne
AU - van der Putten, Louis J.M.
AU - Küsters-Vandevelde, Heidi V.N.
AU - Reijnen, Casper
AU - Colas, Eva
AU - Hausnerová, Jitka
AU - Weinberger, Vit
AU - Snijders, Marc P.L.M.
AU - Vinklerova, Petra
AU - Ravaggi, Antonella
AU - Odicino, Franco
AU - Bignotti, Eliana
AU - McAlpine, Jessica N.
AU - Kruitwagen, Roy
AU - Pijnenborg, Johanna M.A.
N1 - Funding Information:
The authors would like to thank Dr. Astrid Eijkelenboom for her assistance and knowledge within the molecular pathology. The authors are grateful to Dr. Germana Tognon and Dr. Laura Ardighieri for their support in performing molecular classification and helpful discussion of results. The molecular analysis of the Brescia cohort (Italy) was supported by \u201CChiara Andreoli Foundation\u201D.
Publisher Copyright:
© 2024 The Authors
PY - 2025/1/1
Y1 - 2025/1/1
N2 - Objective: The prognostic relevance of hormonal biomarkers in endometrial cancer (EC) has been well-established. A refined three-tiered risk model for estrogen receptor (ER)/progesterone receptor (PR) expression was shown to improve prognostication. This has not been evaluated in relation to the molecular subgroups. This study aimed to evaluate the ER/PR expression within the molecular subgroups in EC. Methods: A retrospective multicenter cohort study was performed and data from the European Network for Individualized Treatment centers and Vancouver, Canada were used. ER/PR immunohistochemical expression was grouped as: ER/PR 0–10 %, 20–80 % or 90–100 %. Molecular subgroups were determined with full next-generation sequencing or combined with immunohistochemistry: POLEmut, mismatch repair deficient (MMRd), p53mut and no-specific molecular profile (NSMP). Results: A total of 739 patients were included (median follow-up 5.0 years). Tumors were classified as POLEmut in 9.1 %(N = 67), MMRd in 27.6 %(N = 204), p53mut in 20.8 %(N = 154) and NSMP in 42.5 %(N = 314). Among all molecular subgroups, patients with ER/PR 90–100 % expression revealed the best disease-specific survival (DSS). Within p53mut, PR 90–100 % expression showed a 5-year DSS of 100.0 %. ER expression is prognostic more relevant in MMRd and NSMP tumors while PR expression in p53mut and NSMP tumors. Across all molecular subgroups, PR 0–10 %, p53mut, lympho-vascular space invasion and FIGO stage III-IV remained independently prognostic for reduced DSS Whereas PR 90–100 % and POLEmut remained independently prognostic for improved DSS. Conclusion: We demonstrated that ER/PR expression remain prognostically relevant within the molecular subgroups, and that a three-tiered cutoff refines prognostication. These data support incorporating routine evaluation of ER/PR expression in clinical practice.
AB - Objective: The prognostic relevance of hormonal biomarkers in endometrial cancer (EC) has been well-established. A refined three-tiered risk model for estrogen receptor (ER)/progesterone receptor (PR) expression was shown to improve prognostication. This has not been evaluated in relation to the molecular subgroups. This study aimed to evaluate the ER/PR expression within the molecular subgroups in EC. Methods: A retrospective multicenter cohort study was performed and data from the European Network for Individualized Treatment centers and Vancouver, Canada were used. ER/PR immunohistochemical expression was grouped as: ER/PR 0–10 %, 20–80 % or 90–100 %. Molecular subgroups were determined with full next-generation sequencing or combined with immunohistochemistry: POLEmut, mismatch repair deficient (MMRd), p53mut and no-specific molecular profile (NSMP). Results: A total of 739 patients were included (median follow-up 5.0 years). Tumors were classified as POLEmut in 9.1 %(N = 67), MMRd in 27.6 %(N = 204), p53mut in 20.8 %(N = 154) and NSMP in 42.5 %(N = 314). Among all molecular subgroups, patients with ER/PR 90–100 % expression revealed the best disease-specific survival (DSS). Within p53mut, PR 90–100 % expression showed a 5-year DSS of 100.0 %. ER expression is prognostic more relevant in MMRd and NSMP tumors while PR expression in p53mut and NSMP tumors. Across all molecular subgroups, PR 0–10 %, p53mut, lympho-vascular space invasion and FIGO stage III-IV remained independently prognostic for reduced DSS Whereas PR 90–100 % and POLEmut remained independently prognostic for improved DSS. Conclusion: We demonstrated that ER/PR expression remain prognostically relevant within the molecular subgroups, and that a three-tiered cutoff refines prognostication. These data support incorporating routine evaluation of ER/PR expression in clinical practice.
KW - Biomarkers
KW - Endometrial carcinoma
KW - Immunohistochemical
KW - Molecular classification
KW - Pathology
KW - Prognosis
U2 - 10.1016/j.ygyno.2024.10.028
DO - 10.1016/j.ygyno.2024.10.028
M3 - Article
SN - 0090-8258
VL - 192
SP - 15
EP - 23
JO - Gynecologic Oncology
JF - Gynecologic Oncology
ER -