Clinical and morphological features of large-cell neuroendocrine carcinomas and small-cell lung carcinomas expressing the DLL3 and ASCL1 oncoproteins

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dc.contributorSistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.authorPRIETO, T. G.
dc.contributor.authorBALDAVIRA, C. M.
dc.contributor.authorMACHADO-RUGOLO, J.
dc.contributor.authorOLIVIERI, E. H. R.
dc.contributor.authorSILVA, E. C. A. da
dc.contributor.authorSILVA, V. G.
dc.contributor.authorABSABER, A. M.
dc.contributor.authorTAKAGAKI, T. Y.
dc.contributor.authorCAPELOZZI, V. L.
dc.date.accessioned2024-02-15T14:53:21Z
dc.date.available2024-02-15T14:53:21Z
dc.date.issued2023
dc.description.abstractIntratumoral similarities and differences between large-cell neuroendocrine carcinomas (LCNECs) and small-cell lung carcinomas (SCLCs) are determined partially by the Notch signaling pathway, which controls the switch from neuroendocrine to slight/non-neuroendocrine cell fate. LCNECs are divided into two subgroups according to genomic alterations: type I LCNECs exhibit a neuroendocrine profile characterized by achaete-scute homolog 1 (ASCL1)high/delta-like protein 3 (DLL3)high/ NOTCHlow and type II LCNECs show the pattern ASCL1low/DLL3low/NOTCHhigh. Here, we used immunohistochemistry, transmission electron microscopy, and digital analysis to examine the role of the Notch ligand DLL3 as an immunomarker of the neuroendocrine state and ASCL1 as a regulator of cell-cell interactions in SCLCs and LCNECs. High DLL3 and ASCL1 expression was associated with atypical submicroscopic characteristics involving nuclear size, chromatin arrangement, Golgi apparatus, and endoplasmic reticulum, and was characteristic of type I LCNECs with similarity to SCLCs, whereas low DLL3 and ASCL1 expression was found in both SCLCs and type II LCNECs. In patients diagnosed at an early stage who did not have metastasis and who underwent chemotherapy, DLL3high and ASCL1high SCLCs and type I LCNECs were associated with a better prognosis and a lower risk of death. The present findings suggested that DLL3/ASCL1 are potential therapeutic targets and prognostic indicators in patients with SCLCs or LCNECs.eng
dc.description.indexMEDLINE
dc.description.indexPubMed
dc.description.indexWoS
dc.description.indexScopus
dc.description.sponsorshipSao Paulo Research Foundation (FAPESP) [2018/20403-6, 2019/12151-0]
dc.description.sponsorshipNational Council for Scientific and Technological Development (CNPq) [303735/2021-0]
dc.description.sponsorshipCoordenacao de Aperfeicoamento de Pessoal de Nivel Superior-Brasil (CAPES) [001]
dc.identifier.citationBRAZILIAN JOURNAL OF MEDICAL AND BIOLOGICAL RESEARCH, v.56, article ID e12921, 8p, 2023
dc.identifier.doi10.1590/1414-431X2023e12921
dc.identifier.eissn1414-431X
dc.identifier.issn0100-879X
dc.identifier.urihttps://observatorio.fm.usp.br/handle/OPI/58051
dc.language.isoeng
dc.publisherASSOC BRAS DIVULG CIENTIFICAeng
dc.relation.ispartofBrazilian Journal of Medical and Biological Research
dc.rightsopenAccesseng
dc.rights.holderCopyright ASSOC BRAS DIVULG CIENTIFICAeng
dc.subjectLarge-cell neuroendocrine carcinomaseng
dc.subjectSmall-cell lung carcinomaseng
dc.subjectImmunohistochemistryeng
dc.subjectDigital analysiseng
dc.subjectTransmission electron microscopyeng
dc.subjectDLL3/ASCL1eng
dc.subject.othernotcheng
dc.subject.othercancereng
dc.subject.wosBiologyeng
dc.subject.wosMedicine, Research & Experimentaleng
dc.titleClinical and morphological features of large-cell neuroendocrine carcinomas and small-cell lung carcinomas expressing the DLL3 and ASCL1 oncoproteinseng
dc.typearticleeng
dc.type.categoryoriginal articleeng
dc.type.versionpublishedVersioneng
dspace.entity.typePublication
hcfmusp.author.externalOLIVIERI, E. H. R.:AC Camargo Canc Ctr, Ctr Int Pesquisa, Sao Paulo, SP, Brazil
hcfmusp.author.externalSILVA, E. C. A. da:Hosp Canc Barretos, Ctr Pesquisa Oncol Mol, Barretos, SP, Brazil
hcfmusp.author.externalSILVA, V. G.:Fundacao Oncocentro Estado Sao Paulo, Sao Paulo, SP, Brazil
hcfmusp.citation.scopus0
hcfmusp.contributor.author-fmusphcTABATHA GUTIERREZ PRIETO MARTINS ROCHA
hcfmusp.contributor.author-fmusphcCAMILA MACHADO BALDAVIRA
hcfmusp.contributor.author-fmusphcJULIANA MACHADO RUGOLO
hcfmusp.contributor.author-fmusphcALEXANDRE MUXFELDT AB'SABER
hcfmusp.contributor.author-fmusphcTERESA YAE TAKAGAKI
hcfmusp.contributor.author-fmusphcVERA LUIZA CAPELOZZI
hcfmusp.description.articlenumbere12921
hcfmusp.description.volume56
hcfmusp.origemWOS
hcfmusp.origem.pubmed38126617
hcfmusp.origem.scopus2-s2.0-85180671053
hcfmusp.origem.wosWOS:001131153100001
hcfmusp.publisher.cityRIBEIRAO PRETOeng
hcfmusp.publisher.countryBRAZILeng
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hcfmusp.scopus.lastupdate2024-05-17
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