Validation of Modaplex POLE mutation assay in endometrial carcinoma

The TCGA-based molecular classification of endometrial cancer has emerged as an important tool to stratify patients according to prognosis. A simplified scheme has been proposed, by using immunohistochemistry for p53, MSH6, and PMS2 and a molecular test for POLE mutations (NGS or Sanger sequencing,...

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Autores: Dorca, Eduard, Velasco, Ana, Varela, Mar, Gatius Calderó, Sònia, Villatoro, Sergio, Fullana, Neus, Cuevas Sánchez, Dolors, Vaquero Susagna, Marta, Birnbaum, Astrid, Neumann, Karsten, Matias-Guiu, Xavier
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Institución:Universitat de Lleida (UdL)
Repositorio:Repositori Obert UdL
OAI Identifier:oai:repositori.udl.cat:10459.1/464628
Acceso en línea:https://doi.org/10.1007/s00428-023-03636-0
https://hdl.handle.net/10459.1/464628
Access Level:acceso abierto
Palabra clave:Endometrial carcinoma
POLE mutation
Molecular classification
Biotype
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spelling Validation of Modaplex POLE mutation assay in endometrial carcinomaDorca, EduardVelasco, AnaVarela, MarGatius Calderó, SòniaVillatoro, SergioFullana, NeusCuevas Sánchez, DolorsVaquero Susagna, MartaBirnbaum, AstridNeumann, KarstenMatias-Guiu, XavierEndometrial carcinomaPOLE mutationMolecular classificationBiotypeThe TCGA-based molecular classification of endometrial cancer has emerged as an important tool to stratify patients according to prognosis. A simplified scheme has been proposed, by using immunohistochemistry for p53, MSH6, and PMS2 and a molecular test for POLE mutations (NGS or Sanger sequencing, techniques that are not available in many centers worldwide). In this study, we validate a novel method that allows simultaneous analysis of multiple pathogenic POLE mutations. The Modaplex technology integrates polymerase chain reaction and capillary electrophoresis. The design of this study encompassed 4 different steps: (1) a retrospective-pilot phase, with 80 tumors, balancing the four molecular subgroups. (2) A retrospective phase of 25 tumors obtained between 2016 and 2020, and 30 tumors obtained between 2000 and 2015. (3) An inter-laboratory corssavalidation step with 19 cases (belonging to phases 1 and 2). (4) A prospective cohort of 123 tumors, of unknown POLE status, with simultaneous validation by Sanger sequencing. A total of 258 samples were analyzed. In the first and second phases, the test showed positive/negative predictive values of 100%, by correctly identifying POLE mutation status in 79/79 and 55/55 cases. Phase 3 showed 100% of inter-laboratory consistency. Phase 4 showed 16 positive samples out of the 123 prospective cases. Overall, the test has revealed sensitivity and specificity of 100%, identifying a total of 47 POLE-mutated tumors. We have shown that this technique allows faster and easier identification of multiple pathogenic POLE mutations with high robustness and confidence when comparing to other tests such as Sanger sequencing.This work was conducted with the contribution of the Carlos III Health Institute (CM20/00110), co-fnanced by the European Regional Development Fund ERDF and supported by Grupos Estables Asociación Española contra el Cancer (GCTRA1804MATI). Modaplex reagents and equipment were provided by Biotype.Springer2023info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://doi.org/10.1007/s00428-023-03636-0https://hdl.handle.net/10459.1/464628reponame:Repositori Obert UdL instname:Universitat de Lleida (UdL)InglésReproducció del document publicat https://doi.org/10.1007/s00428-023-03636-0Virchows Archiv, 2023, vol. 483, p. 787–794cc-by (c) Eduard Dorca et al., 2023Attribution 4.0 Internationalinfo:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by/4.0/oai:repositori.udl.cat:10459.1/4646282026-06-24T12:42:17Z
dc.title.none.fl_str_mv Validation of Modaplex POLE mutation assay in endometrial carcinoma
title Validation of Modaplex POLE mutation assay in endometrial carcinoma
spellingShingle Validation of Modaplex POLE mutation assay in endometrial carcinoma
Dorca, Eduard
Endometrial carcinoma
POLE mutation
Molecular classification
Biotype
title_short Validation of Modaplex POLE mutation assay in endometrial carcinoma
title_full Validation of Modaplex POLE mutation assay in endometrial carcinoma
title_fullStr Validation of Modaplex POLE mutation assay in endometrial carcinoma
title_full_unstemmed Validation of Modaplex POLE mutation assay in endometrial carcinoma
title_sort Validation of Modaplex POLE mutation assay in endometrial carcinoma
dc.creator.none.fl_str_mv Dorca, Eduard
Velasco, Ana
Varela, Mar
Gatius Calderó, Sònia
Villatoro, Sergio
Fullana, Neus
Cuevas Sánchez, Dolors
Vaquero Susagna, Marta
Birnbaum, Astrid
Neumann, Karsten
Matias-Guiu, Xavier
author Dorca, Eduard
author_facet Dorca, Eduard
Velasco, Ana
Varela, Mar
Gatius Calderó, Sònia
Villatoro, Sergio
Fullana, Neus
Cuevas Sánchez, Dolors
Vaquero Susagna, Marta
Birnbaum, Astrid
Neumann, Karsten
Matias-Guiu, Xavier
author_role author
author2 Velasco, Ana
Varela, Mar
Gatius Calderó, Sònia
Villatoro, Sergio
Fullana, Neus
Cuevas Sánchez, Dolors
Vaquero Susagna, Marta
Birnbaum, Astrid
Neumann, Karsten
Matias-Guiu, Xavier
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Endometrial carcinoma
POLE mutation
Molecular classification
Biotype
topic Endometrial carcinoma
POLE mutation
Molecular classification
Biotype
description The TCGA-based molecular classification of endometrial cancer has emerged as an important tool to stratify patients according to prognosis. A simplified scheme has been proposed, by using immunohistochemistry for p53, MSH6, and PMS2 and a molecular test for POLE mutations (NGS or Sanger sequencing, techniques that are not available in many centers worldwide). In this study, we validate a novel method that allows simultaneous analysis of multiple pathogenic POLE mutations. The Modaplex technology integrates polymerase chain reaction and capillary electrophoresis. The design of this study encompassed 4 different steps: (1) a retrospective-pilot phase, with 80 tumors, balancing the four molecular subgroups. (2) A retrospective phase of 25 tumors obtained between 2016 and 2020, and 30 tumors obtained between 2000 and 2015. (3) An inter-laboratory corssavalidation step with 19 cases (belonging to phases 1 and 2). (4) A prospective cohort of 123 tumors, of unknown POLE status, with simultaneous validation by Sanger sequencing. A total of 258 samples were analyzed. In the first and second phases, the test showed positive/negative predictive values of 100%, by correctly identifying POLE mutation status in 79/79 and 55/55 cases. Phase 3 showed 100% of inter-laboratory consistency. Phase 4 showed 16 positive samples out of the 123 prospective cases. Overall, the test has revealed sensitivity and specificity of 100%, identifying a total of 47 POLE-mutated tumors. We have shown that this technique allows faster and easier identification of multiple pathogenic POLE mutations with high robustness and confidence when comparing to other tests such as Sanger sequencing.
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/10.1007/s00428-023-03636-0
https://hdl.handle.net/10459.1/464628
url https://doi.org/10.1007/s00428-023-03636-0
https://hdl.handle.net/10459.1/464628
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat https://doi.org/10.1007/s00428-023-03636-0
Virchows Archiv, 2023, vol. 483, p. 787–794
dc.rights.none.fl_str_mv cc-by (c) Eduard Dorca et al., 2023
Attribution 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/4.0/
rights_invalid_str_mv cc-by (c) Eduard Dorca et al., 2023
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Springer
publisher.none.fl_str_mv Springer
dc.source.none.fl_str_mv reponame:Repositori Obert UdL
instname:Universitat de Lleida (UdL)
instname_str Universitat de Lleida (UdL)
reponame_str Repositori Obert UdL
collection Repositori Obert UdL
repository.name.fl_str_mv
repository.mail.fl_str_mv
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