Relationship between the expressions of DLL3, ASC1, TTF-1 and Ki-67: First steps of precision medicine at SCLC

Autores
Silva, Samuel; Sousa, Juliana C.; Nogueira, Cleto; Feijo, Raquel; Martins Neto, Francisco; Cardoso Marinho, Laura; Sousa, Guilherme; Denninghoff, Valeria Cecilia; Tavora, Fabio
Año de publicación
2024
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
This study presents an observational, cross-sectional analysis of 64 patients diagnosed with small cell lung cancer (SCLC) at a reference laboratory for thoracic pathology between 2022 and 2024. The primary objective was to evaluate the expression of Delta-like ligand 3 (DLL3) and other neuroendocrine markers such as Chromogranin, and Synaptophysin, utilizing both traditional immunohistochemistry and digital pathology tools. Patients were primarily older adults, with a median age of over 71, and most biopsies were obtained from lung parenchyma. Immunohistochemistry (IHC) was performed using specific monoclonal antibodies, with DLL3 showing variable expression across the samples. Notably, DLL3 was expressed in 72.3% of the cases, with varied intensities and a semi-quantitative H-score applied for more nuanced analysis. ASCL1 was expressed in 97% of cases, with the majority considered low-expressors. Only 11% had high expression. TTF-1, traditionally not a conventional marker for the diagnosis of SCLC, was positive in half of the cases, suggesting its potential as a biomarker. The study underscores the significant variability in the expression of neuroendocrine markers in SCLC, with implications for both diagnosis and potential therapeutic targeting. DLL3, particularly, shows promise as a therapeutic target due to its high expression rate in the cohort. The use of digital pathology software QuPath enhanced the accuracy and depth of analysis, allowing for detailed morphometric analysis and potentially informing more personalized treatment approaches. The findings emphasize the need for further research into the role of these markers in the management and treatment of SCLC, considering the poor prognosis and high mortality rate observed in the cohort.
Fil: Silva, Samuel. Universidade Federal Do Ceara; Brasil. ARGOS Laboratory; Brasil
Fil: Sousa, Juliana C.. ARGOS Laboratory; Brasil
Fil: Nogueira, Cleto. Universidade Federal Do Ceara; Brasil. ARGOS Laboratory; Brasil
Fil: Feijo, Raquel. Universidade Federal Do Ceara; Brasil. Messejana Heart and Lung Hospital; Brasil
Fil: Martins Neto, Francisco. Messejana Heart and Lung Hospital; Brasil
Fil: Cardoso Marinho, Laura. Universidade Federal Do Ceara; Brasil. ARGOS Laboratory; Brasil
Fil: Sousa, Guilherme. ARGOS Laboratory; Brasil
Fil: Denninghoff, Valeria Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Centro de Educación Médica e Investigaciones Clínicas "Norberto Quirno"; Argentina. Universidad de Granada; España
Fil: Tavora, Fabio. Universidade Federal Do Ceara; Brasil. ARGOS Laboratory; Brasil
Materia
DLL3
SCLC
Immunohistochemestry
Tissue
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/262177
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/262177
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Relationship between the expressions of DLL3, ASC1, TTF-1 and Ki-67: First steps of precision medicine at SCLCSilva, SamuelSousa, Juliana C.Nogueira, CletoFeijo, RaquelMartins Neto, FranciscoCardoso Marinho, LauraSousa, GuilhermeDenninghoff, Valeria CeciliaTavora, FabioDLL3SCLCImmunohistochemestryTissuehttps://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3This study presents an observational, cross-sectional analysis of 64 patients diagnosed with small cell lung cancer (SCLC) at a reference laboratory for thoracic pathology between 2022 and 2024. The primary objective was to evaluate the expression of Delta-like ligand 3 (DLL3) and other neuroendocrine markers such as Chromogranin, and Synaptophysin, utilizing both traditional immunohistochemistry and digital pathology tools. Patients were primarily older adults, with a median age of over 71, and most biopsies were obtained from lung parenchyma. Immunohistochemistry (IHC) was performed using specific monoclonal antibodies, with DLL3 showing variable expression across the samples. Notably, DLL3 was expressed in 72.3% of the cases, with varied intensities and a semi-quantitative H-score applied for more nuanced analysis. ASCL1 was expressed in 97% of cases, with the majority considered low-expressors. Only 11% had high expression. TTF-1, traditionally not a conventional marker for the diagnosis of SCLC, was positive in half of the cases, suggesting its potential as a biomarker. The study underscores the significant variability in the expression of neuroendocrine markers in SCLC, with implications for both diagnosis and potential therapeutic targeting. DLL3, particularly, shows promise as a therapeutic target due to its high expression rate in the cohort. The use of digital pathology software QuPath enhanced the accuracy and depth of analysis, allowing for detailed morphometric analysis and potentially informing more personalized treatment approaches. The findings emphasize the need for further research into the role of these markers in the management and treatment of SCLC, considering the poor prognosis and high mortality rate observed in the cohort.Fil: Silva, Samuel. Universidade Federal Do Ceara; Brasil. ARGOS Laboratory; BrasilFil: Sousa, Juliana C.. ARGOS Laboratory; BrasilFil: Nogueira, Cleto. Universidade Federal Do Ceara; Brasil. ARGOS Laboratory; BrasilFil: Feijo, Raquel. Universidade Federal Do Ceara; Brasil. Messejana Heart and Lung Hospital; BrasilFil: Martins Neto, Francisco. Messejana Heart and Lung Hospital; BrasilFil: Cardoso Marinho, Laura. Universidade Federal Do Ceara; Brasil. ARGOS Laboratory; BrasilFil: Sousa, Guilherme. ARGOS Laboratory; BrasilFil: Denninghoff, Valeria Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Centro de Educación Médica e Investigaciones Clínicas "Norberto Quirno"; Argentina. Universidad de Granada; EspañaFil: Tavora, Fabio. Universidade Federal Do Ceara; Brasil. ARGOS Laboratory; BrasilImpact Journals2024-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/262177Silva, Samuel; Sousa, Juliana C.; Nogueira, Cleto; Feijo, Raquel; Martins Neto, Francisco; et al.; Relationship between the expressions of DLL3, ASC1, TTF-1 and Ki-67: First steps of precision medicine at SCLC; Impact Journals; Oncotarget; 15; 1; 10-2024; 750-7631949-2553CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.oncotarget.com/lookup/doi/10.18632/oncotarget.28660info:eu-repo/semantics/altIdentifier/doi/10.18632/oncotarget.28660info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:40:12Zoai:ri.conicet.gov.ar:11336/262177instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:40:12.523CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Relationship between the expressions of DLL3, ASC1, TTF-1 and Ki-67: First steps of precision medicine at SCLC
title Relationship between the expressions of DLL3, ASC1, TTF-1 and Ki-67: First steps of precision medicine at SCLC
spellingShingle Relationship between the expressions of DLL3, ASC1, TTF-1 and Ki-67: First steps of precision medicine at SCLC
Silva, Samuel
DLL3
SCLC
Immunohistochemestry
Tissue
title_short Relationship between the expressions of DLL3, ASC1, TTF-1 and Ki-67: First steps of precision medicine at SCLC
title_full Relationship between the expressions of DLL3, ASC1, TTF-1 and Ki-67: First steps of precision medicine at SCLC
title_fullStr Relationship between the expressions of DLL3, ASC1, TTF-1 and Ki-67: First steps of precision medicine at SCLC
title_full_unstemmed Relationship between the expressions of DLL3, ASC1, TTF-1 and Ki-67: First steps of precision medicine at SCLC
title_sort Relationship between the expressions of DLL3, ASC1, TTF-1 and Ki-67: First steps of precision medicine at SCLC
dc.creator.none.fl_str_mv Silva, Samuel
Sousa, Juliana C.
Nogueira, Cleto
Feijo, Raquel
Martins Neto, Francisco
Cardoso Marinho, Laura
Sousa, Guilherme
Denninghoff, Valeria Cecilia
Tavora, Fabio
author Silva, Samuel
author_facet Silva, Samuel
Sousa, Juliana C.
Nogueira, Cleto
Feijo, Raquel
Martins Neto, Francisco
Cardoso Marinho, Laura
Sousa, Guilherme
Denninghoff, Valeria Cecilia
Tavora, Fabio
author_role author
author2 Sousa, Juliana C.
Nogueira, Cleto
Feijo, Raquel
Martins Neto, Francisco
Cardoso Marinho, Laura
Sousa, Guilherme
Denninghoff, Valeria Cecilia
Tavora, Fabio
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv DLL3
SCLC
Immunohistochemestry
Tissue
topic DLL3
SCLC
Immunohistochemestry
Tissue
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.2
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv This study presents an observational, cross-sectional analysis of 64 patients diagnosed with small cell lung cancer (SCLC) at a reference laboratory for thoracic pathology between 2022 and 2024. The primary objective was to evaluate the expression of Delta-like ligand 3 (DLL3) and other neuroendocrine markers such as Chromogranin, and Synaptophysin, utilizing both traditional immunohistochemistry and digital pathology tools. Patients were primarily older adults, with a median age of over 71, and most biopsies were obtained from lung parenchyma. Immunohistochemistry (IHC) was performed using specific monoclonal antibodies, with DLL3 showing variable expression across the samples. Notably, DLL3 was expressed in 72.3% of the cases, with varied intensities and a semi-quantitative H-score applied for more nuanced analysis. ASCL1 was expressed in 97% of cases, with the majority considered low-expressors. Only 11% had high expression. TTF-1, traditionally not a conventional marker for the diagnosis of SCLC, was positive in half of the cases, suggesting its potential as a biomarker. The study underscores the significant variability in the expression of neuroendocrine markers in SCLC, with implications for both diagnosis and potential therapeutic targeting. DLL3, particularly, shows promise as a therapeutic target due to its high expression rate in the cohort. The use of digital pathology software QuPath enhanced the accuracy and depth of analysis, allowing for detailed morphometric analysis and potentially informing more personalized treatment approaches. The findings emphasize the need for further research into the role of these markers in the management and treatment of SCLC, considering the poor prognosis and high mortality rate observed in the cohort.
Fil: Silva, Samuel. Universidade Federal Do Ceara; Brasil. ARGOS Laboratory; Brasil
Fil: Sousa, Juliana C.. ARGOS Laboratory; Brasil
Fil: Nogueira, Cleto. Universidade Federal Do Ceara; Brasil. ARGOS Laboratory; Brasil
Fil: Feijo, Raquel. Universidade Federal Do Ceara; Brasil. Messejana Heart and Lung Hospital; Brasil
Fil: Martins Neto, Francisco. Messejana Heart and Lung Hospital; Brasil
Fil: Cardoso Marinho, Laura. Universidade Federal Do Ceara; Brasil. ARGOS Laboratory; Brasil
Fil: Sousa, Guilherme. ARGOS Laboratory; Brasil
Fil: Denninghoff, Valeria Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Centro de Educación Médica e Investigaciones Clínicas "Norberto Quirno"; Argentina. Universidad de Granada; España
Fil: Tavora, Fabio. Universidade Federal Do Ceara; Brasil. ARGOS Laboratory; Brasil
description This study presents an observational, cross-sectional analysis of 64 patients diagnosed with small cell lung cancer (SCLC) at a reference laboratory for thoracic pathology between 2022 and 2024. The primary objective was to evaluate the expression of Delta-like ligand 3 (DLL3) and other neuroendocrine markers such as Chromogranin, and Synaptophysin, utilizing both traditional immunohistochemistry and digital pathology tools. Patients were primarily older adults, with a median age of over 71, and most biopsies were obtained from lung parenchyma. Immunohistochemistry (IHC) was performed using specific monoclonal antibodies, with DLL3 showing variable expression across the samples. Notably, DLL3 was expressed in 72.3% of the cases, with varied intensities and a semi-quantitative H-score applied for more nuanced analysis. ASCL1 was expressed in 97% of cases, with the majority considered low-expressors. Only 11% had high expression. TTF-1, traditionally not a conventional marker for the diagnosis of SCLC, was positive in half of the cases, suggesting its potential as a biomarker. The study underscores the significant variability in the expression of neuroendocrine markers in SCLC, with implications for both diagnosis and potential therapeutic targeting. DLL3, particularly, shows promise as a therapeutic target due to its high expression rate in the cohort. The use of digital pathology software QuPath enhanced the accuracy and depth of analysis, allowing for detailed morphometric analysis and potentially informing more personalized treatment approaches. The findings emphasize the need for further research into the role of these markers in the management and treatment of SCLC, considering the poor prognosis and high mortality rate observed in the cohort.
publishDate 2024
dc.date.none.fl_str_mv 2024-10
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/262177
Silva, Samuel; Sousa, Juliana C.; Nogueira, Cleto; Feijo, Raquel; Martins Neto, Francisco; et al.; Relationship between the expressions of DLL3, ASC1, TTF-1 and Ki-67: First steps of precision medicine at SCLC; Impact Journals; Oncotarget; 15; 1; 10-2024; 750-763
1949-2553
CONICET Digital
CONICET
url http://hdl.handle.net/11336/262177
identifier_str_mv Silva, Samuel; Sousa, Juliana C.; Nogueira, Cleto; Feijo, Raquel; Martins Neto, Francisco; et al.; Relationship between the expressions of DLL3, ASC1, TTF-1 and Ki-67: First steps of precision medicine at SCLC; Impact Journals; Oncotarget; 15; 1; 10-2024; 750-763
1949-2553
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.oncotarget.com/lookup/doi/10.18632/oncotarget.28660
info:eu-repo/semantics/altIdentifier/doi/10.18632/oncotarget.28660
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Impact Journals
publisher.none.fl_str_mv Impact Journals
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.070432

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