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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art_MACHADO-RUGOLO_Concomitant_TP53_mutation_in_earlystage_resected_EGFRmutated_nonsmall_2023.PDF (392.85 KB)
Citações na Scopus
1
Tipo de produção
article
Data de publicação
2023
DOI
SciELO
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
ASSOC BRAS DIVULG CIENTIFICA
Autores
OLIVIERI, E. H. R.
FABRO, A. T.
RAINHO, C. A.
CASTELLI, E. C.
RIBOLLA, P. E. M.
Citação
BRAZILIAN JOURNAL OF MEDICAL AND BIOLOGICAL RESEARCH, v.56, article ID e12488, 11p, 2023
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
TP53 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.
Palavras-chave
Non-small-cell lung cancer (NSCLC), Epidermal growth factor receptor (EGFR), Tumor protein 53 (TP53), Mutation, Survival
URI
https://observatorio.fm.usp.br/handle/OPI/53880
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Coleções
Artigos e Materiais de Revistas Científicas - FM/MDR
Artigos e Materiais de Revistas Científicas - FM/MPT
Artigos e Materiais de Revistas Científicas - HC/ICHC
Artigos e Materiais de Revistas Científicas - HC/InCor
Artigos e Materiais de Revistas Científicas - LIM/03
Artigos e Materiais de Revistas Científicas - LIM/09
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