Concomitant TP53 mutation in early-stage resected EGFR-mutated non-small cell lung cancer: a narrative approach in a genetically admixed Brazilian cohort

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dc.contributor.authorMachado-Rugolo, J. [UNESP]
dc.contributor.authorBaldavira, C. M.
dc.contributor.authorPrieto, T. G.
dc.contributor.authorOlivieri, E. H.R.
dc.contributor.authorFabro, A. T.
dc.contributor.authorRainho, C. A. [UNESP]
dc.contributor.authorCastelli, E. C. [UNESP]
dc.contributor.authorRibolla, P. E.M. [UNESP]
dc.contributor.authorAb’saber, A. M.
dc.contributor.authorTakagaki, T.
dc.contributor.authorNagai, M. A.
dc.contributor.authorCapelozzi, V. L.
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.contributor.institutionUniversidade Estadual Paulista (UNESP)
dc.contributor.institutionAC Camargo Cancer Center
dc.contributor.institutionInstituto do Câncer de São Paulo
dc.date.accessioned2023-07-29T13:50:49Z
dc.date.available2023-07-29T13:50:49Z
dc.date.issued2023-01-01
dc.description.abstractTP53 mutations are frequent in non-small cell lung cancer (NSCLC) and have been associated with poor outcome. The prognostic and predictive relevance of EGFR/TP53 co-mutations in NSCLC is controversial. We analyzed lung tissue specimens from 70 patients with NSCLC using next-generation sequencing to determine EGFR and TP53 status and the association between these status with baseline patient and tumor characteristics, adjuvant treatments, relapse, and progression-free (PFS) and overall survival (OS) after surgical resection. We found the EGFR mutation in 32.9% of patients (20% classical mutations and 12.9% uncommon mutations). TP53 missense mutations occurred in 25.7% and TP53/EGFR co-mutations occurred in 43.5% of patients. Stage after surgical resection was significantly associated with OS (P=0.028). We identified an association between progression-free survival and poor outcome in patients with distant metastases (P=0.007). We found a marginally significant difference in OS between genders (P=0.057) and between mutant and wild type TP53 (P=0.079). In univariate analysis, distant metastases (P=0.027), pathological stage (IIIA-IIIB vs I-II; P=0.028), and TP53 status (borderline significance between wild type and mutant; P=0.079) influenced OS. In multivariable analysis, a significant model for high risk of death and poor OS (P=0.029) selected patients in stage IIIA-IIIB, with relapse and distant metastases, non-responsive to platin-based chemotherapy and erlotinib, with tumors harboring EGFR uncommon mutations, with TP53 mutant, and with EGFR/TP53 co-mutations. Our study suggested that TP53 mutation tends to confer poor survival and a potentially negative predictive effect associated with a non-response to platinum-based chemotherapy and erlotinib in early-stage resected EGFR-mutated NSCLC.en
dc.description.affiliationLaboratório de Histomorfometria e Genômica Pulmonar Departamento de Patologia Faculdade de Medicina Universidade de São Paulo, SP
dc.description.affiliationCentro de Avaliac¸ão de Tecnologias em Saúde Hospital das Clínicas da Faculdade de Medicina de Botucatu Universidade Estadual Paulista, SP
dc.description.affiliationCentro Internacional de Pesquisa/CIPE AC Camargo Cancer Center, São Paulo, SP
dc.description.affiliationDepartamento de Patologia e Medicina Legal Laboratório de Medicina Respiratória Faculdade de Medicina de Ribeirão Preto Universidade de São Paulo, SP
dc.description.affiliationInstituto de Biociências Departamento de Ciências Químicas e Biológicas Universidade Estadual Paulista, SP
dc.description.affiliationLaboratório de Genética Molecular e Bioinformática Unidade de Pesquisa Experimental Faculdade de Medicina Universidade Estadual Paulista, SP
dc.description.affiliationDepartamento de Patologia Faculdade de Medicina Universidade Estadual Paulista, SP
dc.description.affiliationInstituto de Biotecnologia Universidade Estadual Paulista, SP
dc.description.affiliationInstituto de Biociências Departamento de Bioestatística Biologia Vegetal Parasitologia e Zoologia Universidade Estadual Paulista, SP
dc.description.affiliationDivisão de Pneumologia Instituto do Corac¸ão Faculdade de Medicina Universidade de São Paulo, SP
dc.description.affiliationDepartamento de Radiologia e Oncologia Faculdade de Medicina Universidade de São Paulo, SP
dc.description.affiliationLaboratório de Genética Molecular Centro de Pesquisa Translacional em Oncologia Instituto do Câncer de São Paulo, SP
dc.description.affiliationUnespCentro de Avaliac¸ão de Tecnologias em Saúde Hospital das Clínicas da Faculdade de Medicina de Botucatu Universidade Estadual Paulista, SP
dc.description.affiliationUnespInstituto de Biociências Departamento de Ciências Químicas e Biológicas Universidade Estadual Paulista, SP
dc.description.affiliationUnespLaboratório de Genética Molecular e Bioinformática Unidade de Pesquisa Experimental Faculdade de Medicina Universidade Estadual Paulista, SP
dc.description.affiliationUnespDepartamento de Patologia Faculdade de Medicina Universidade Estadual Paulista, SP
dc.description.affiliationUnespInstituto de Biotecnologia Universidade Estadual Paulista, SP
dc.description.affiliationUnespInstituto de Biociências Departamento de Bioestatística Biologia Vegetal Parasitologia e Zoologia Universidade Estadual Paulista, SP
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipIdCAPES: 001
dc.description.sponsorshipIdCNPq: 303735/2021-0
dc.identifierhttp://dx.doi.org/10.1590/1414-431X2023e12488
dc.identifier.citationBrazilian Journal of Medical and Biological Research, v. 56.
dc.identifier.doi10.1590/1414-431X2023e12488
dc.identifier.issn1414-431X
dc.identifier.scopus2-s2.0-85152474794
dc.identifier.urihttp://hdl.handle.net/11449/248687
dc.language.isoeng
dc.relation.ispartofBrazilian Journal of Medical and Biological Research
dc.sourceScopus
dc.subjectEpidermal growth factor receptor (EGFR)
dc.subjectMutation
dc.subjectNon-small-cell lung cancer (NSCLC)
dc.subjectSurvival
dc.subjectTumor protein 53 (TP53)
dc.titleConcomitant TP53 mutation in early-stage resected EGFR-mutated non-small cell lung cancer: a narrative approach in a genetically admixed Brazilian cohorten
dc.typeArtigo

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