Evaluation of somatic mutations in cervicovaginal samples as a non-invasive method for the detection and molecular classification of endometrial cancer

Background: The incidence of endometrial cancer is increasing worldwide. While delays in diagnosis reduce survival, case molecular misclassification might be associated with under- and over-treatment. The objective of this study was to evaluate genetic alterations to detect and molecularly classify...

ver descrição completa

Detalhes bibliográficos
Autores: Pelegrina, Beatriz, Paytubi, Sonia, Marin, Fátima, Martínez, José Manuel, Carmona, Álvaro, Frias-Gomez, Jon, Peremiquel-Trillas, Paula, Dorca, Eduard, Zanca, Alba, López-Querol, Marta, Onieva Hernández, Irene, Benavente, Yolanda, Barahona, Marc, Fernandez-Gonzalez, Sergi, de Francisco, Javier, Caño, Víctor, Vidal, August, Pijuan, Lara, Canet-Hermida, Júlia, Dueñas, Núria, Brunet, Joan, Pineda, Marta, Matias-Guiu, Xavier, Ponce, Jordi, Bosch, Francesc Xavier, de Sanjosé, Silvia, Alemany, Laia, Costas, Laura
Tipo de documento: artigo
Estado:Versão publicada
Data de publicação:2023
País:España
Recursos:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositório:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10459.1/467660
Acesso em linha:https://doi.org/10.1016/j.ebiom.2023.10471
https://hdl.handle.net/10459.1/467660
Access Level:Acceso aberto
Palavra-chave:Endometrial neoplasms
Early detection of cancer
Papanicolaou test
Mutation
Biomarkers
id ES_c071e9606506fdf30428596d56a3ddea
oai_identifier_str oai:recercat.cat:10459.1/467660
network_acronym_str ES
network_name_str España
repository_id_str
spelling Evaluation of somatic mutations in cervicovaginal samples as a non-invasive method for the detection and molecular classification of endometrial cancerPelegrina, BeatrizPaytubi, SoniaMarin, FátimaMartínez, José ManuelCarmona, ÁlvaroFrias-Gomez, JonPeremiquel-Trillas, PaulaDorca, EduardZanca, AlbaLópez-Querol, MartaOnieva Hernández, IreneBenavente, YolandaBarahona, MarcFernandez-Gonzalez, Sergide Francisco, JavierCaño, VíctorVidal, AugustPijuan, LaraCanet-Hermida, JúliaDueñas, NúriaBrunet, JoanPineda, MartaMatias-Guiu, XavierPonce, JordiBosch, Francesc Xavierde Sanjosé, SilviaAlemany, LaiaCostas, LauraEndometrial neoplasmsEarly detection of cancerPapanicolaou testMutationBiomarkersBackground: The incidence of endometrial cancer is increasing worldwide. While delays in diagnosis reduce survival, case molecular misclassification might be associated with under- and over-treatment. The objective of this study was to evaluate genetic alterations to detect and molecularly classify cases of endometrial cancer using non-invasive samples. Methods: Consecutive patients with incident endometrial cancer (N = 139) and controls (N = 107) from a recent Spanish case-control study were included in this analysis. Overall, 339 cervicovaginal samples (out of which 228 were clinician-collected and 111 were self-collected) were analysed using a test based on next-generation sequencing (NGS), which targets 47 genes. Immunohistochemical markers were evaluated in 133 tumour samples. A total of 159 samples were used to train the detection algorithm and 180 samples were used for validation. Findings: Overall, 73% (N = 94 out of 129 clinician-collected samples, and N = 66 out of 90 self-collected samples) of endometrial cancer cases had detectable mutations in clinician-collected and self-collected samples, while the specificity was 80% (79/99) for clinician-collected samples and 90% (19/21) for self-collected samples. The molecular classifications obtained using tumour samples and non-invasive gynaecologic samples in our study showed moderate-to-good agreement. The molecular classification of cases of endometrial cancer into four groups using NGS of both clinician-collected and self-collected cervicovaginal samples yielded significant differences in disease-free survival. The cases with mutations in POLE had an excellent prognosis, whereas the cases with TP53 mutations had the poorest clinical outcome, which is consistent with the data on tumour samples. Interpretation: This study classified endometrial cancer cases into four molecular groups based on the analysis of cervicovaginal samples that showed significant differences in disease-free survival. The molecular classification of endometrial cancer in non-invasive samples may improve patient care and survival by indicating the early need for aggressive surgery, as well as reducing referrals to highly specialized hospitals in cancers with good prognosis. Validation in independent sets will confirm the potential for molecular classification in non-invasive samples.Elsevier2023info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://doi.org/10.1016/j.ebiom.2023.10471https://hdl.handle.net/10459.1/467660reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.1016/j.ebiom.2023.10471EBioMedicine, 2023, vol. 94, 104716cc-by-nc-nd (c)The Authors, 2023Attribution-NonCommercial-NoDerivatives 4.0 Internationalinfo:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by-nc-nd/4.0/oai:recercat.cat:10459.1/4676602026-05-29T05:05:01Z
dc.title.none.fl_str_mv Evaluation of somatic mutations in cervicovaginal samples as a non-invasive method for the detection and molecular classification of endometrial cancer
title Evaluation of somatic mutations in cervicovaginal samples as a non-invasive method for the detection and molecular classification of endometrial cancer
spellingShingle Evaluation of somatic mutations in cervicovaginal samples as a non-invasive method for the detection and molecular classification of endometrial cancer
Pelegrina, Beatriz
Endometrial neoplasms
Early detection of cancer
Papanicolaou test
Mutation
Biomarkers
title_short Evaluation of somatic mutations in cervicovaginal samples as a non-invasive method for the detection and molecular classification of endometrial cancer
title_full Evaluation of somatic mutations in cervicovaginal samples as a non-invasive method for the detection and molecular classification of endometrial cancer
title_fullStr Evaluation of somatic mutations in cervicovaginal samples as a non-invasive method for the detection and molecular classification of endometrial cancer
title_full_unstemmed Evaluation of somatic mutations in cervicovaginal samples as a non-invasive method for the detection and molecular classification of endometrial cancer
title_sort Evaluation of somatic mutations in cervicovaginal samples as a non-invasive method for the detection and molecular classification of endometrial cancer
dc.creator.none.fl_str_mv Pelegrina, Beatriz
Paytubi, Sonia
Marin, Fátima
Martínez, José Manuel
Carmona, Álvaro
Frias-Gomez, Jon
Peremiquel-Trillas, Paula
Dorca, Eduard
Zanca, Alba
López-Querol, Marta
Onieva Hernández, Irene
Benavente, Yolanda
Barahona, Marc
Fernandez-Gonzalez, Sergi
de Francisco, Javier
Caño, Víctor
Vidal, August
Pijuan, Lara
Canet-Hermida, Júlia
Dueñas, Núria
Brunet, Joan
Pineda, Marta
Matias-Guiu, Xavier
Ponce, Jordi
Bosch, Francesc Xavier
de Sanjosé, Silvia
Alemany, Laia
Costas, Laura
author Pelegrina, Beatriz
author_facet Pelegrina, Beatriz
Paytubi, Sonia
Marin, Fátima
Martínez, José Manuel
Carmona, Álvaro
Frias-Gomez, Jon
Peremiquel-Trillas, Paula
Dorca, Eduard
Zanca, Alba
López-Querol, Marta
Onieva Hernández, Irene
Benavente, Yolanda
Barahona, Marc
Fernandez-Gonzalez, Sergi
de Francisco, Javier
Caño, Víctor
Vidal, August
Pijuan, Lara
Canet-Hermida, Júlia
Dueñas, Núria
Brunet, Joan
Pineda, Marta
Matias-Guiu, Xavier
Ponce, Jordi
Bosch, Francesc Xavier
de Sanjosé, Silvia
Alemany, Laia
Costas, Laura
author_role author
author2 Paytubi, Sonia
Marin, Fátima
Martínez, José Manuel
Carmona, Álvaro
Frias-Gomez, Jon
Peremiquel-Trillas, Paula
Dorca, Eduard
Zanca, Alba
López-Querol, Marta
Onieva Hernández, Irene
Benavente, Yolanda
Barahona, Marc
Fernandez-Gonzalez, Sergi
de Francisco, Javier
Caño, Víctor
Vidal, August
Pijuan, Lara
Canet-Hermida, Júlia
Dueñas, Núria
Brunet, Joan
Pineda, Marta
Matias-Guiu, Xavier
Ponce, Jordi
Bosch, Francesc Xavier
de Sanjosé, Silvia
Alemany, Laia
Costas, Laura
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Endometrial neoplasms
Early detection of cancer
Papanicolaou test
Mutation
Biomarkers
topic Endometrial neoplasms
Early detection of cancer
Papanicolaou test
Mutation
Biomarkers
description Background: The incidence of endometrial cancer is increasing worldwide. While delays in diagnosis reduce survival, case molecular misclassification might be associated with under- and over-treatment. The objective of this study was to evaluate genetic alterations to detect and molecularly classify cases of endometrial cancer using non-invasive samples. Methods: Consecutive patients with incident endometrial cancer (N = 139) and controls (N = 107) from a recent Spanish case-control study were included in this analysis. Overall, 339 cervicovaginal samples (out of which 228 were clinician-collected and 111 were self-collected) were analysed using a test based on next-generation sequencing (NGS), which targets 47 genes. Immunohistochemical markers were evaluated in 133 tumour samples. A total of 159 samples were used to train the detection algorithm and 180 samples were used for validation. Findings: Overall, 73% (N = 94 out of 129 clinician-collected samples, and N = 66 out of 90 self-collected samples) of endometrial cancer cases had detectable mutations in clinician-collected and self-collected samples, while the specificity was 80% (79/99) for clinician-collected samples and 90% (19/21) for self-collected samples. The molecular classifications obtained using tumour samples and non-invasive gynaecologic samples in our study showed moderate-to-good agreement. The molecular classification of cases of endometrial cancer into four groups using NGS of both clinician-collected and self-collected cervicovaginal samples yielded significant differences in disease-free survival. The cases with mutations in POLE had an excellent prognosis, whereas the cases with TP53 mutations had the poorest clinical outcome, which is consistent with the data on tumour samples. Interpretation: This study classified endometrial cancer cases into four molecular groups based on the analysis of cervicovaginal samples that showed significant differences in disease-free survival. The molecular classification of endometrial cancer in non-invasive samples may improve patient care and survival by indicating the early need for aggressive surgery, as well as reducing referrals to highly specialized hospitals in cancers with good prognosis. Validation in independent sets will confirm the potential for molecular classification in non-invasive samples.
publishDate 2023
dc.date.none.fl_str_mv 2023
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://doi.org/10.1016/j.ebiom.2023.10471
https://hdl.handle.net/10459.1/467660
url https://doi.org/10.1016/j.ebiom.2023.10471
https://hdl.handle.net/10459.1/467660
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1016/j.ebiom.2023.10471
EBioMedicine, 2023, vol. 94, 104716
dc.rights.none.fl_str_mv cc-by-nc-nd (c)The Authors, 2023
Attribution-NonCommercial-NoDerivatives 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
rights_invalid_str_mv cc-by-nc-nd (c)The Authors, 2023
Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869418477888995328
score 15.812429

Registros relacionados