Relevance of Molecular Profiling in Patients With Low-Grade
Endometrial Cancer

J 2022

Relevance of Molecular Profiling in Patients With Low-Grade Endometrial Cancer

VREDE, Stephanie W., Jenneke KASIUS, Johan BULTEN, Steven TEERENSTRA, Jutta HUVILA et. al.

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

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30214 Obstetrics and gynaecology

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

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

Abstract

V originále

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.

Citovat

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.

@article{2241362,
   author = {Vrede, Stephanie W. and Kasius, Jenneke and Bulten, Johan and Teerenstra, Steven and Huvila, Jutta and Colas, Eva and GilandMoreno, Antonio and Boll, Dorry and Vos, Maria Caroline and van Altena, Anne M. and Asberger, Jasmin and Sweegers, Sanne and van Weelden, Willem Jan van and van der Putten, Louis J. M. and Amant, Frédéric and Visser, Nicole C. M. and Snijders, Marc P. L. M. and KüstersandVandevelde, Heidi V. N. and Kruitwagen, Roy and MatiasandGuiu, Xavier and Weinberger, Vít and Reijnen, Casper and Pijnenborg, Johanna M. A.},
   article_location = {CHICAGO},
   article_number = {12},
   doi = {http://dx.doi.org/10.1001/jamanetworkopen.2022.47372},
   keywords = {Low-Grade Endometrial Cancer; Molecular Profiling},
   language = {eng},
   issn = {2574-3805},
   journal = {JAMA network open},
   title = {Relevance of Molecular Profiling in Patients With Low-Grade Endometrial Cancer},
   url = {https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2799631},
   volume = {5},
   year = {2022}
}

TY  - JOUR
ID  - 2241362
AU  - Vrede, Stephanie W. - Kasius, Jenneke - Bulten, Johan - Teerenstra, Steven - Huvila, Jutta - Colas, Eva - Gil-Moreno, Antonio - Boll, Dorry - Vos, Maria Caroline - van Altena, Anne M. - Asberger, Jasmin - Sweegers, Sanne - van Weelden, Willem Jan van - van der Putten, Louis J. M. - Amant, Frédéric - Visser, Nicole C. M. - Snijders, Marc P. L. M. - Küsters-Vandevelde, Heidi V. N. - Kruitwagen, Roy - Matias-Guiu, Xavier - Weinberger, Vít - Reijnen, Casper - Pijnenborg, Johanna M. A.
PY  - 2022
TI  - Relevance of Molecular Profiling in Patients With Low-Grade Endometrial Cancer
JF  - JAMA network open
VL  - 5
IS  - 12
SP  - 1-10
EP  - 1-10
PB  - AMER MEDICAL ASSOC
SN  - 25743805
KW  - Low-Grade Endometrial Cancer
KW  - Molecular Profiling
UR  - https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2799631
N2  - 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.
ER  -

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. \textit{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.

Detailed Information on Publication Record