Tomoyuki Naito1, Hibiki Udagawa2, Shigeki Umemura3, Tetsuya Sakai3, Yoshitaka Zenke3, Keisuke Kirita3, Shingo Matsumoto3, Kiyotaka Yoh3, Seiji Niho3, Masahiro Tsuboi4, Genichiro Ishii5, Koichi Goto3. 1. Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Japan; Division of Pathology, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center Hospital East, Kashiwa, Japan. 2. Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Japan. Electronic address: hudagawa@east.ncc.go.jp. 3. Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Japan. 4. Department of Thoracic Surgery, National Cancer Center Hospital East, Kashiwa, Japan. 5. Division of Pathology, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center Hospital East, Kashiwa, Japan. Electronic address: gishii@east.ncc.go.jp.
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 AND METHODS: 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%, P < 0.01). In stage I NSCLC, SWI/SNF-Loss (n = 23) was associated with shorter overall survival (HR: 2.43; 95% CI: 1.18-5.01; P = 0.01) and recurrence-free survival (HR: 2.22; 95% CI: 1.17-4.24; P < 0.01) compared to BAF-Intact (n = 563). The degree of TMB was significantly higher among NSCLC patients with BAF-Loss (n = 3) than BAF-Intact (n = 7) (median 437 vs 113 mutations/whole-exome, P = 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.
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 AND METHODS: 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 NSCLCpatients with BAF-Loss than BAF-Intact (42% vs 26%, P < 0.01). In stage I NSCLC, SWI/SNF-Loss (n = 23) was associated with shorter overall survival (HR: 2.43; 95% CI: 1.18-5.01; P = 0.01) and recurrence-free survival (HR: 2.22; 95% CI: 1.17-4.24; P < 0.01) compared to BAF-Intact (n = 563). The degree of TMB was significantly higher among NSCLCpatients with BAF-Loss (n = 3) than BAF-Intact (n = 7) (median 437 vs 113 mutations/whole-exome, P = 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.
Authors: Anthony M Musolf; Claire L Simpson; Bilal A Moiz; Claudio W Pikielny; Candace D Middlebrooks; Diptasri Mandal; Mariza de Andrade; Michael D Cole; Colette Gaba; Ping Yang; Ming You; Yafang Li; Elena Y Kupert; Marshall W Anderson; Ann G Schwartz; Susan M Pinney; Christopher I Amos; Joan E Bailey-Wilson Journal: Cancer Res Date: 2021-04-14 Impact factor: 13.312