VREDE, Stephanie W., Jenneke KASIUS, Johan BULTEN, Steven TEERENSTRA, Jutta HUVILA, Eva COLAS, Antonio GIL-MORENO, Dorry BOLL, Maria Caroline VOS, Anne M. VAN ALTENA, Jasmin ASBERGER, Sanne SWEEGERS, Willem Jan van VAN WEELDEN, Louis J. M. VAN DER PUTTEN, Frédéric AMANT, Nicole C. M. VISSER, Marc P. L. M. SNIJDERS, Heidi V. N. KÜSTERS-VANDEVELDE, Roy KRUITWAGEN, Xavier MATIAS-GUIU, Vít WEINBERGER, Casper REIJNEN and Johanna M. A. PIJNENBORG. Relevance of Molecular Profiling in Patients With Low-Grade Endometrial Cancer. JAMA network open. CHICAGO: AMER MEDICAL ASSOC, 2022, vol. 5, No 12, p. 1-10. ISSN 2574-3805. Available from: https://dx.doi.org/10.1001/jamanetworkopen.2022.47372.
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Basic information
Original name Relevance of Molecular Profiling in Patients With Low-Grade Endometrial Cancer
Authors VREDE, Stephanie W., Jenneke KASIUS, Johan BULTEN, Steven TEERENSTRA, Jutta HUVILA, Eva COLAS, Antonio GIL-MORENO, Dorry BOLL, Maria Caroline VOS, Anne M. VAN ALTENA, Jasmin ASBERGER, Sanne SWEEGERS, Willem Jan van VAN WEELDEN, Louis J. M. VAN DER PUTTEN, Frédéric AMANT, Nicole C. M. VISSER, Marc P. L. M. SNIJDERS, Heidi V. N. KÜSTERS-VANDEVELDE, Roy KRUITWAGEN, Xavier MATIAS-GUIU, Vít WEINBERGER (203 Czech Republic, belonging to the institution), Casper REIJNEN and Johanna M. A. PIJNENBORG (guarantor).
Edition JAMA network open, CHICAGO, AMER MEDICAL ASSOC, 2022, 2574-3805.
Other information
Original language English
Type of outcome Article in a journal
Field of Study 30214 Obstetrics and gynaecology
Country of publisher United States of America
Confidentiality degree is not subject to a state or trade secret
WWW URL
Impact factor Impact factor: 13.800
RIV identification code RIV/00216224:14110/22:00127562
Organization unit Faculty of Medicine
Doi http://dx.doi.org/10.1001/jamanetworkopen.2022.47372
UT WoS 000919589300010
Keywords in English Low-Grade Endometrial Cancer; Molecular Profiling
Tags 14110411, rivok
Tags International impact, Reviewed
Changed by Changed by: Mgr. Tereza Miškechová, učo 341652. Changed: 24/2/2023 10:41.
Abstract
Importance 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. Objective To determine the association of molecular profiling with outcomes among patients with low-grade EC. Design, Setting, and Participants 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. Exposures Molecular testing of the 4 molecular subgroups. Main Outcomes and Measures The main outcome was disease-specific survival (DSS) within the molecular subgroups. Results 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. Conclusions and Relevance 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.
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