Prognostic stratification of endometrial cancers with high microsatellite instability or no specific molecular profile
ObjectiveTo identify high-risk disease in clinicopathologic low-risk endometrial cancer (EC) with high microsatellite instability (MSI-H) or no specific molecular profile (NSMP) and therapeutic insensitivity in clinicopathologic high-risk MSI-H/NSMP EC.MethodsWe searched The Cancer Genome Atlas for...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-05-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2023.1105504/full |
| _version_ | 1797821974991339520 |
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| author | Jesus Gonzalez-Bosquet S. John Weroha Jamie N. Bakkum-Gamez Amy L. Weaver Michaela E. McGree Sean C. Dowdy Abimbola O. Famuyide Benjamin R. Kipp Kevin C. Halling Siddhartha Yadav Fergus J. Couch Fergus J. Couch Karl C. Podratz |
| author_facet | Jesus Gonzalez-Bosquet S. John Weroha Jamie N. Bakkum-Gamez Amy L. Weaver Michaela E. McGree Sean C. Dowdy Abimbola O. Famuyide Benjamin R. Kipp Kevin C. Halling Siddhartha Yadav Fergus J. Couch Fergus J. Couch Karl C. Podratz |
| author_sort | Jesus Gonzalez-Bosquet |
| collection | DOAJ |
| description | ObjectiveTo identify high-risk disease in clinicopathologic low-risk endometrial cancer (EC) with high microsatellite instability (MSI-H) or no specific molecular profile (NSMP) and therapeutic insensitivity in clinicopathologic high-risk MSI-H/NSMP EC.MethodsWe searched The Cancer Genome Atlas for DNA sequencing, RNA expression, and surveillance data regarding MSI-H/NSMP EC. We used a molecular classification system of E2F1 and CCNA2 expression and sequence variations in POLE, PPP2R1A, or FBXW7 (ECPPF) to prognostically stratify MSI-H/NSMP ECs. Clinical outcomes were annotated after integrating ECPPF and sequence variations in homologous recombination (HR) genes.ResultsData were available for 239 patients with EC, which included 58 MSI-H and 89 NSMP cases. ECPPF effectively stratified MSI-H/NSMP EC into distinct molecular groups with prognostic implications: molecular low risk (MLR), with low CCNA2 and E2F1 expression, and molecular high risk (MHR), with high CCNA2 and E2F1 expression and/or PPP2R1A and/or FBXW7 variants. The 3-year disease-free survival (DFS) rate was 43.8% in the MHR group with clinicopathologic low-risk indicators and 93.9% in the MLR group (P<.001). In the MHR group, wild-type HR genes were present in 28% of cases but in 81% of documented recurrences. The 3-year DFS rate in patients with MSI-H/NSMP EC with clinicopathologic high-risk indicators was significantly higher in the MLR (94.1%) and MHR/HR variant gene (88.9%) groups than in the MHR/HR wild-type gene group (50.3%, P<.001).ConclusionECPPF may resolve prognostic challenges for MSI-H/NSMP EC by identifying occult high-risk disease in EC with clinicopathologic low-risk indicators and therapeutic insensitivity in EC with clinicopathologic high-risk indicators. |
| first_indexed | 2024-03-13T10:01:00Z |
| format | Article |
| id | doaj.art-32b034603ff54448b98bb03612a864b7 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-03-13T10:01:00Z |
| publishDate | 2023-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-32b034603ff54448b98bb03612a864b72023-05-23T05:10:22ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2023-05-011310.3389/fonc.2023.11055041105504Prognostic stratification of endometrial cancers with high microsatellite instability or no specific molecular profileJesus Gonzalez-Bosquet0S. John Weroha1Jamie N. Bakkum-Gamez2Amy L. Weaver3Michaela E. McGree4Sean C. Dowdy5Abimbola O. Famuyide6Benjamin R. Kipp7Kevin C. Halling8Siddhartha Yadav9Fergus J. Couch10Fergus J. Couch11Karl C. Podratz12Department of Obstetrics and Gynecology, University of Iowa, Iowa City, IA, United StatesDivision of Medical Oncology, Mayo Clinic, Rochester, MN, United StatesDepartment of Obstetrics and Gynecology, Mayo Clinic, Rochester, MN, United StatesDepartment of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, United StatesDepartment of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, United StatesDepartment of Obstetrics and Gynecology, Mayo Clinic, Rochester, MN, United StatesDepartment of Obstetrics and Gynecology, Mayo Clinic, Rochester, MN, United StatesDepartment of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, United StatesDepartment of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, United StatesDivision of Medical Oncology, Mayo Clinic, Rochester, MN, United StatesDepartment of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, United StatesDepartment of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, United StatesDepartment of Obstetrics and Gynecology, Mayo Clinic, Rochester, MN, United StatesObjectiveTo identify high-risk disease in clinicopathologic low-risk endometrial cancer (EC) with high microsatellite instability (MSI-H) or no specific molecular profile (NSMP) and therapeutic insensitivity in clinicopathologic high-risk MSI-H/NSMP EC.MethodsWe searched The Cancer Genome Atlas for DNA sequencing, RNA expression, and surveillance data regarding MSI-H/NSMP EC. We used a molecular classification system of E2F1 and CCNA2 expression and sequence variations in POLE, PPP2R1A, or FBXW7 (ECPPF) to prognostically stratify MSI-H/NSMP ECs. Clinical outcomes were annotated after integrating ECPPF and sequence variations in homologous recombination (HR) genes.ResultsData were available for 239 patients with EC, which included 58 MSI-H and 89 NSMP cases. ECPPF effectively stratified MSI-H/NSMP EC into distinct molecular groups with prognostic implications: molecular low risk (MLR), with low CCNA2 and E2F1 expression, and molecular high risk (MHR), with high CCNA2 and E2F1 expression and/or PPP2R1A and/or FBXW7 variants. The 3-year disease-free survival (DFS) rate was 43.8% in the MHR group with clinicopathologic low-risk indicators and 93.9% in the MLR group (P<.001). In the MHR group, wild-type HR genes were present in 28% of cases but in 81% of documented recurrences. The 3-year DFS rate in patients with MSI-H/NSMP EC with clinicopathologic high-risk indicators was significantly higher in the MLR (94.1%) and MHR/HR variant gene (88.9%) groups than in the MHR/HR wild-type gene group (50.3%, P<.001).ConclusionECPPF may resolve prognostic challenges for MSI-H/NSMP EC by identifying occult high-risk disease in EC with clinicopathologic low-risk indicators and therapeutic insensitivity in EC with clinicopathologic high-risk indicators.https://www.frontiersin.org/articles/10.3389/fonc.2023.1105504/fullCCNA2ECPPFE2F1endometrial cancerFBXW7MSI |
| spellingShingle | Jesus Gonzalez-Bosquet S. John Weroha Jamie N. Bakkum-Gamez Amy L. Weaver Michaela E. McGree Sean C. Dowdy Abimbola O. Famuyide Benjamin R. Kipp Kevin C. Halling Siddhartha Yadav Fergus J. Couch Fergus J. Couch Karl C. Podratz Prognostic stratification of endometrial cancers with high microsatellite instability or no specific molecular profile Frontiers in Oncology CCNA2 ECPPF E2F1 endometrial cancer FBXW7 MSI |
| title | Prognostic stratification of endometrial cancers with high microsatellite instability or no specific molecular profile |
| title_full | Prognostic stratification of endometrial cancers with high microsatellite instability or no specific molecular profile |
| title_fullStr | Prognostic stratification of endometrial cancers with high microsatellite instability or no specific molecular profile |
| title_full_unstemmed | Prognostic stratification of endometrial cancers with high microsatellite instability or no specific molecular profile |
| title_short | Prognostic stratification of endometrial cancers with high microsatellite instability or no specific molecular profile |
| title_sort | prognostic stratification of endometrial cancers with high microsatellite instability or no specific molecular profile |
| topic | CCNA2 ECPPF E2F1 endometrial cancer FBXW7 MSI |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2023.1105504/full |
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