Molecular characterization of mixed-histology endometrial carcinoma provides prognostic and therapeutic value over morphologic findings
Abstract We performed molecular analysis of a single-institution cohort of clinically diagnosed mixed-histology endometrial carcinoma (MEC). A gynecologic pathologist confirmed that 72 cases met diagnostic criteria for MEC based on WHO 2020 guidelines, and these were molecularly classified using bot...
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| Format: | Article |
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Nature Portfolio
2025-02-01
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| Series: | npj Precision Oncology |
| Online Access: | https://doi.org/10.1038/s41698-025-00803-1 |
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| author | Paulina J. Haight Ashwini Esnakula Courtney J. Riedinger Adrian A. Suarez Jessica Gillespie Ashley Patton Alexis Chassen David E. Cohn Casey M. Cosgrove |
| author_facet | Paulina J. Haight Ashwini Esnakula Courtney J. Riedinger Adrian A. Suarez Jessica Gillespie Ashley Patton Alexis Chassen David E. Cohn Casey M. Cosgrove |
| author_sort | Paulina J. Haight |
| collection | DOAJ |
| description | Abstract We performed molecular analysis of a single-institution cohort of clinically diagnosed mixed-histology endometrial carcinoma (MEC). A gynecologic pathologist confirmed that 72 cases met diagnostic criteria for MEC based on WHO 2020 guidelines, and these were molecularly classified using both a DNA-based and histologic approach. Tumors were classified as: POLE-mutated (13.9%), microsatellite instability (MSI)-high/mismatch repair deficient (MMRd) (26.4%), TP53/p53 abnormal (p53abnl) (48.6%), no specific molecular profile (NSMP) (11.1%). Recurrence risk significantly differed based upon molecular class, but not histology. 44% of MEC cases had a HER2 IHC score of 2–3+, and this was not limited to p53abnl tumors. Transcriptional analysis demonstrated 93 differentially expressed genes between p53abnl and NSMP tumors, including many associated with the innate immune response and DNA damage repair. While p53abnl and NSMP tumors have similarly poor outcomes, transcriptome analysis revealed biologic differences that could impact targeted therapeutics in this high-risk group. |
| format | Article |
| id | doaj-art-9d2ae9e283bd41d8a96816ec9076a2aa |
| institution | Kabale University |
| issn | 2397-768X |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Precision Oncology |
| spelling | doaj-art-9d2ae9e283bd41d8a96816ec9076a2aa2025-02-09T12:09:28ZengNature Portfolionpj Precision Oncology2397-768X2025-02-019111210.1038/s41698-025-00803-1Molecular characterization of mixed-histology endometrial carcinoma provides prognostic and therapeutic value over morphologic findingsPaulina J. Haight0Ashwini Esnakula1Courtney J. Riedinger2Adrian A. Suarez3Jessica Gillespie4Ashley Patton5Alexis Chassen6David E. Cohn7Casey M. Cosgrove8Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, The Ohio State University Wexner Medical Center, The James Cancer Hospital and Solove Research InstituteDepartment of Pathology, The Ohio State University Wexner Medical CenterDivision of Gynecologic Oncology, Department of Obstetrics and Gynecology, The Ohio State University Wexner Medical Center, The James Cancer Hospital and Solove Research InstituteDepartment of Pathology, The Ohio State University Wexner Medical CenterDivision of Gynecologic Oncology, Department of Obstetrics and Gynecology, The Ohio State University Wexner Medical Center, The James Cancer Hospital and Solove Research InstituteDepartment of Pathology, The Ohio State University Wexner Medical CenterDivision of Gynecologic Oncology, Department of Obstetrics and Gynecology, The Ohio State University Wexner Medical Center, The James Cancer Hospital and Solove Research InstituteDivision of Gynecologic Oncology, Department of Obstetrics and Gynecology, The Ohio State University Wexner Medical Center, The James Cancer Hospital and Solove Research InstituteDivision of Gynecologic Oncology, Department of Obstetrics and Gynecology, The Ohio State University Wexner Medical Center, The James Cancer Hospital and Solove Research InstituteAbstract We performed molecular analysis of a single-institution cohort of clinically diagnosed mixed-histology endometrial carcinoma (MEC). A gynecologic pathologist confirmed that 72 cases met diagnostic criteria for MEC based on WHO 2020 guidelines, and these were molecularly classified using both a DNA-based and histologic approach. Tumors were classified as: POLE-mutated (13.9%), microsatellite instability (MSI)-high/mismatch repair deficient (MMRd) (26.4%), TP53/p53 abnormal (p53abnl) (48.6%), no specific molecular profile (NSMP) (11.1%). Recurrence risk significantly differed based upon molecular class, but not histology. 44% of MEC cases had a HER2 IHC score of 2–3+, and this was not limited to p53abnl tumors. Transcriptional analysis demonstrated 93 differentially expressed genes between p53abnl and NSMP tumors, including many associated with the innate immune response and DNA damage repair. While p53abnl and NSMP tumors have similarly poor outcomes, transcriptome analysis revealed biologic differences that could impact targeted therapeutics in this high-risk group.https://doi.org/10.1038/s41698-025-00803-1 |
| spellingShingle | Paulina J. Haight Ashwini Esnakula Courtney J. Riedinger Adrian A. Suarez Jessica Gillespie Ashley Patton Alexis Chassen David E. Cohn Casey M. Cosgrove Molecular characterization of mixed-histology endometrial carcinoma provides prognostic and therapeutic value over morphologic findings npj Precision Oncology |
| title | Molecular characterization of mixed-histology endometrial carcinoma provides prognostic and therapeutic value over morphologic findings |
| title_full | Molecular characterization of mixed-histology endometrial carcinoma provides prognostic and therapeutic value over morphologic findings |
| title_fullStr | Molecular characterization of mixed-histology endometrial carcinoma provides prognostic and therapeutic value over morphologic findings |
| title_full_unstemmed | Molecular characterization of mixed-histology endometrial carcinoma provides prognostic and therapeutic value over morphologic findings |
| title_short | Molecular characterization of mixed-histology endometrial carcinoma provides prognostic and therapeutic value over morphologic findings |
| title_sort | molecular characterization of mixed histology endometrial carcinoma provides prognostic and therapeutic value over morphologic findings |
| url | https://doi.org/10.1038/s41698-025-00803-1 |
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