Non-small cell lung cancer with loss of expression of the SWI/SNF complex is associated with aggressive clinicopathological features, PD-L1-positive status, and high tumor mutation burden.
Lung Cancer
; 138: 35-42, 2019 12.
Article
em En
| MEDLINE
| ID: mdl-31630044
ABSTRACT
OBJECTIVES:
Loss of the chromatin remodeling SWItch/Sucrose Non-fermentable (SWI/SNF) complex is implicated in the pathogenesis of several types of neoplasms. The aim of this study was to examine the clinicopathological features of non-small cell lung cancer (NSCLC) with loss of expression of the SWI/SNF complex. MATERIALS ANDMETHODS:
Specimens from a total 1013 NSCLC cases used for tissue microarrays (TMAs) were immunohistochemically examined for expression of SWI/SNF complex (BAF) subunits, namely SMARCA4, SMARCA2, ARID1A, and ARID1B. We examined the clinicopathological features and PD-L1 expression status in NSCLC cases with loss of expression of one or more subunits of the SWI/SNF complex (BAF-Loss). Moreover, we compared the tumor mutation burden (TMB) between NSCLC cases with BAF-Loss and those with intact expression of the four subunits (BAF-Intact).RESULTS:
Using TMA, BAF-Loss was observed in 5.4% of cases (SMARCA4 2.4%, SMARCA2 2.4%, ARID1A 1.3%, and ARID1B 0.3%). Concurrent loss of expression of two or more subunits of the SWI/SNF complex was detected in 0.7% of cases. BAF-Loss was significantly associated with smoking history, young age, male sex, pulmonary emphysema/bullae, large invasive tumor size, pleural invasion, vascular invasion, solid-predominant morphology, and absence of a lepidic growth component. A higher proportion of PD-L1-positive cases was observed among NSCLC patients with BAF-Loss than BAF-Intact (42% vs 26%, Pâ¯<â¯0.01). In stage I NSCLC, SWI/SNF-Loss (nâ¯=â¯23) was associated with shorter overall survival (HR 2.43; 95% CI 1.18-5.01; Pâ¯=â¯0.01) and recurrence-free survival (HR 2.22; 95% CI 1.17-4.24; Pâ¯<â¯0.01) compared to BAF-Intact (nâ¯=â¯563). The degree of TMB was significantly higher among NSCLC patients with BAF-Loss (nâ¯=â¯3) than BAF-Intact (nâ¯=â¯7) (median 437 vs 113 mutations/whole-exome, Pâ¯=â¯0.02).CONCLUSION:
The current results suggest that loss of SWI/SNF expression in NSCLC is associated with aggressive clinicopathological features, PD-L1-positive status and high TMB.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
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Proteínas Nucleares
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Carcinoma Pulmonar de Células não Pequenas
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DNA Helicases
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Proteínas de Ligação a DNA
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Antígeno B7-H1
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Neoplasias Pulmonares
Tipo de estudo:
Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Adult
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Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Lung Cancer
Ano de publicação:
2019
Tipo de documento:
Article