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

• Published in: Lung cancer (Amsterdam, Netherlands) Netherlands), 2019-12, Vol.138, p.35-42
• Main Authors: Naito, Tomoyuki, Udagawa, Hibiki, Umemura, Shigeki, Sakai, Tetsuya, Zenke, Yoshitaka, Kirita, Keisuke, Matsumoto, Shingo, Yoh, Kiyotaka, Niho, Seiji, Tsuboi, Masahiro, Ishii, Genichiro, Goto, Koichi
• Format: Article
• Language: English
• Subjects: Clinicopathological feature; PD-L1 expression; SWI/SNF complex; Tissue microarray; Tumor mutation burden
• ISSN: 0169-5002; 1872-8332
• DOI: 10.1016/j.lungcan.2019.10.009

•SWI/SNF is a chromatin remodeling complex that regulates gene expression.•We evaluated expression of SWI/SNF subunits in NSCLC using immunohistochemistry.•Loss of expression of the SWI/SNF complex was observed in 5.5% of 1013 NSCLC cases.•NSCLC with loss of SWI/SNF showed aggressive clinicopathological features.•PD-L1-positivity and tumor mutation burden are higher in NSCLC with loss of SWI/SNF. 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. 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). 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