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Hormonal biomarkers remain prognostically relevant within the molecular subgroups in endometrial cancer
SW. Vrede, WJ. Van Weelden, J. Bulten, CB. Gilks, S. Teerenstra, J. Huvila, X. Matias-Guiu, A. Gil-Moreno, J. Asberger, S. Sweegers, LJM. van der Putten, HVN. Küsters-Vandevelde, C. Reijnen, E. Colas, J. Hausnerová, V. Weinberger, MPLM. Snijders,...
Language English Country United States
Document type Journal Article, Multicenter Study
- MeSH
- Adult MeSH
- Immunohistochemistry MeSH
- Cohort Studies MeSH
- Middle Aged MeSH
- Humans MeSH
- Biomarkers, Tumor * metabolism genetics MeSH
- Tumor Suppressor Protein p53 metabolism genetics MeSH
- Endometrial Neoplasms * metabolism pathology genetics mortality MeSH
- Prognosis MeSH
- Receptors, Estrogen * metabolism biosynthesis MeSH
- Receptors, Progesterone * metabolism biosynthesis MeSH
- Retrospective Studies MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
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.
Department of Health Evidence Radboud university medical center Nijmegen the Netherlands
Department of Obstetrics and Gynecology Canisius Wilhelmina Hospital Nijmegen the Netherlands
Department of Obstetrics and Gynecology Medical Center University of Freiburg Freiburg Germany
Department of Obstetrics and Gynecology Radboud University Medical Center Nijmegen the Netherlands
Department of Pathology Canisius Wilhelmina Hospital Nijmegen the Netherlands
Department of Pathology Radboud university Medical Center Nijmegen the Netherlands
Department of Pathology University Hospital in Brno and Masaryk University Brno Czech Republic
Department of Pathology University of Turku Turku Finland
Department of Radiation Oncology Radboud University Medical Center Nijmegen the Netherlands
Gynecological Department Vall Hebron University Hospital CIBERONC Barcelona Spain
References provided by Crossref.org
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- $a Vrede, Stephanie W $u Department of Obstetrics and Gynecology, Radboud University Medical Center, Nijmegen, the Netherlands; Department of Obstetrics and Gynecology, Canisius-Wilhelmina Hospital, Nijmegen, the Netherlands. Electronic address: stephanie.vrede@radboudumc.nl
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- $a Hormonal biomarkers remain prognostically relevant within the molecular subgroups in endometrial cancer / $c SW. Vrede, WJ. Van Weelden, J. Bulten, CB. Gilks, S. Teerenstra, J. Huvila, X. Matias-Guiu, A. Gil-Moreno, J. Asberger, S. Sweegers, LJM. van der Putten, HVN. Küsters-Vandevelde, C. Reijnen, E. Colas, J. Hausnerová, V. Weinberger, MPLM. Snijders, P. Vinklerova, A. Ravaggi, F. Odicino, E. Bignotti, JN. McAlpine, R. Kruitwagen, JMA. Pijnenborg
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- $a 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.
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