{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["5(12)"],"submitter":["Vrede SW"],"pubmed_abstract":["<h4>Importance</h4>Patients with low-grade (ie, grade 1-2) endometrial cancer (EC) are characterized by their favorable prognosis compared with patients with high-grade (ie, grade 3) EC. With the implementation of molecular profiling, the prognostic relevance of tumor grading might lose attention. As most patients present with low-grade EC and have an excellent outcome, the value of molecular profiling for these patients is unclear.<h4>Objective</h4>To determine the association of molecular profiling with outcomes among patients with low-grade EC.<h4>Design, setting, and participants</h4>This retrospective cohort study included a multicenter international European cohort of patients diagnosed with EC between 1994 and 2018, with a median follow-up of 5.9 years. Molecular subgroups were determined by next-generation sequencing using single-molecule molecular inversion probes and by immunohistochemistry. Subsequently, tumors were classified as polymerase epsilon (POLE)-altered, microsatellite instable (MSI), tumor protein p53 (TP53)-altered, or no specific molecular profile (NSMP). Patients diagnosed with any histological subtypes and FIGO (International Federation of Gynecology and Obstetrics) stages of EC were included, but patients with early-stage EC (FIGO I-II) were only included if they had known lymph node status. Data were analyzed February 20 to June 16, 2022.<h4>Exposures</h4>Molecular testing of the 4 molecular subgroups.<h4>Main outcomes and measures</h4>The main outcome was disease-specific survival (DSS) within the molecular subgroups.<h4>Results</h4>A total of 393 patients with EC were included, with a median (range) age of 64.0 (31.0-86.0) years and median (range) body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) of 29.1 (18.0-58.3). Most patients presented with early-stage (290 patients [73.8%]) and low-grade (209 patients [53.2%]) disease. Of all patients, 33 (8.4%) had POLE-altered EC, 78 (19.8%) had MSI EC, 72 (18.3%) had TP53-altered EC, and 210 (53.4%) had NSMP EC. Across all molecular subgroups, patients with low-grade EC had superior 5-year DSS compared with those with high-grade EC, varying between 90% to 100% vs 41% to 90% (P < .001). Multivariable analysis in the entire cohort including age, tumor grade, FIGO stage, lymphovascular space invasion, and the molecular subgroups as covariates found that only high-grade (hazard ratio [HR], 4.29; 95% CI, 2.15-8.53; P < .001), TP53-altered (HR, 1.76; 95% CI, 1.04-2.95; P = .03), and FIGO stage III or IV (HR, 4.26; 95% CI, 2.50-7.26; P < .001) disease were independently associated with reduced DSS.<h4>Conclusions and relevance</h4>This cohort study found that patients with low-grade EC had an excellent prognosis independent of molecular subgroup. These findings do not support routine molecular profiling in patients with low-grade EC, and they demonstrate the importance of primary diagnostic tumor grading and selective profiling in low-grade EC to increase cost-effectiveness."],"journal":["JAMA network open"],"pagination":["e2247372"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9856566"],"repository":["biostudies-literature"],"pubmed_title":["Relevance of Molecular Profiling in Patients With Low-Grade Endometrial Cancer."],"pmcid":["PMC9856566"],"pubmed_authors":["van der Putten LJM","Weinberger V","Kasius J","Sweegers S","Snijders MPLM","van Weelden WJ","Reijnen C","Bulten J","Kruitwagen R","Vos MC","van Altena AM","Pijnenborg JMA","Vrede SW","Asberger J","Gil-Moreno A","Matias-Guiu X","Kusters-Vandevelde HVN","Visser NCM","Teerenstra S","Huvila J","Colas E","Amant F","Boll D"],"additional_accession":[]},"is_claimable":false,"name":"Relevance of Molecular Profiling in Patients With Low-Grade Endometrial Cancer.","description":"<h4>Importance</h4>Patients with low-grade (ie, grade 1-2) endometrial cancer (EC) are characterized by their favorable prognosis compared with patients with high-grade (ie, grade 3) EC. With the implementation of molecular profiling, the prognostic relevance of tumor grading might lose attention. As most patients present with low-grade EC and have an excellent outcome, the value of molecular profiling for these patients is unclear.<h4>Objective</h4>To determine the association of molecular profiling with outcomes among patients with low-grade EC.<h4>Design, setting, and participants</h4>This retrospective cohort study included a multicenter international European cohort of patients diagnosed with EC between 1994 and 2018, with a median follow-up of 5.9 years. Molecular subgroups were determined by next-generation sequencing using single-molecule molecular inversion probes and by immunohistochemistry. Subsequently, tumors were classified as polymerase epsilon (POLE)-altered, microsatellite instable (MSI), tumor protein p53 (TP53)-altered, or no specific molecular profile (NSMP). Patients diagnosed with any histological subtypes and FIGO (International Federation of Gynecology and Obstetrics) stages of EC were included, but patients with early-stage EC (FIGO I-II) were only included if they had known lymph node status. Data were analyzed February 20 to June 16, 2022.<h4>Exposures</h4>Molecular testing of the 4 molecular subgroups.<h4>Main outcomes and measures</h4>The main outcome was disease-specific survival (DSS) within the molecular subgroups.<h4>Results</h4>A total of 393 patients with EC were included, with a median (range) age of 64.0 (31.0-86.0) years and median (range) body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) of 29.1 (18.0-58.3). Most patients presented with early-stage (290 patients [73.8%]) and low-grade (209 patients [53.2%]) disease. Of all patients, 33 (8.4%) had POLE-altered EC, 78 (19.8%) had MSI EC, 72 (18.3%) had TP53-altered EC, and 210 (53.4%) had NSMP EC. Across all molecular subgroups, patients with low-grade EC had superior 5-year DSS compared with those with high-grade EC, varying between 90% to 100% vs 41% to 90% (P < .001). Multivariable analysis in the entire cohort including age, tumor grade, FIGO stage, lymphovascular space invasion, and the molecular subgroups as covariates found that only high-grade (hazard ratio [HR], 4.29; 95% CI, 2.15-8.53; P < .001), TP53-altered (HR, 1.76; 95% CI, 1.04-2.95; P = .03), and FIGO stage III or IV (HR, 4.26; 95% CI, 2.50-7.26; P < .001) disease were independently associated with reduced DSS.<h4>Conclusions and relevance</h4>This cohort study found that patients with low-grade EC had an excellent prognosis independent of molecular subgroup. These findings do not support routine molecular profiling in patients with low-grade EC, and they demonstrate the importance of primary diagnostic tumor grading and selective profiling in low-grade EC to increase cost-effectiveness.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Dec","modification":"2026-05-27T11:05:26.211Z","creation":"2025-02-19T00:13:34.294Z"},"accession":"S-EPMC9856566","cross_references":{"pubmed":["36525269"],"doi":["10.1001/jamanetworkopen.2022.47372"]}}