Epidemiologic and clinicopathological characteristics of SMARCA4-deficient non–small cell lung cancer form a single center in Yunnan, China.

Abstract

e20771 Background: SMARCA4-deficient non-small cell lung cancer (SMARCA4-d NSCLC) is an aggressive subtype with poorly defined geographic epidemiology. Yunnan Province is a lung cancer high-risk area with unique etiological factors. The characteristics of SMARCA4-d NSCLC in this region are unknown. Methods: We retrospectively identified SMARCA4-d NSCLC (confirmed by BRG1 IHC loss) from 3124 consecutive NSCLC cases at Yunnan Cancer Hospital (06/2025-11/2025). Clinicopathological data, IHC profiles, and imaging data were analyzed. This cohort forms the basis of an ongoing expanded multicenter study in Yunnan incorporating longitudinal follow-up, treatment response evaluation, and multi-omics profiling. Results: 40 SMARCA4-d NSCLC cases (approximately 1% prevalence) were identified. Patients were predominantly male (95.0%) with a male-to-female ratio of 19:1, 81.5% smokers (31/38) , with a median age of 63.5 years, and geographically clustered in high-incidence mining areas such as Kunming, Qujing City, and Honghe Prefecture . The right upper lobe was the most common primary site.SMARCA4-deficient NSCLC are characterized by bulky primary tumors, lymph node involvement, and distant spread. They show a particular predilection for retroperitoneal lymph node and adrenal metastases compared to typical NSCLC.Importantly, even upper-lobe tumors frequently involve station 7 and 10 lymph nodes. This pattern indicates unique biological behavior in the Yunnan population, which merits further exploration. IHC showed a heterogeneous/null phenotype: TTF-1+ (35.3%), Napsin A+ (16.1%), CK5/6+ (36.1%), P40+ (20.5%)(Table 1), with a high median Ki-67 index (60%). Conclusions: We report the unique clinicopathological profile of SMARCA4-d NSCLC in Yunnan, characterized by a specific high-risk demographic, heterogeneous immunophenotype, high proliferation, and a novel predilection for downward metastatic spread. These findings warrant enhanced abdominal staging awareness in this population. Our ongoing multicenter validation, coupled with planned deep molecular and microenvironmental characterization, aims to define the biological drivers of this aggressive variant and explore its therapeutic vulnerabilities. IHC profiles of SMARCA4-deficient non-small cell lung cancer in yunnan. Marker Positive Negative Unknown SMARCA4/BRG-1 0 (0%) 40 (100%) 0 (0%) TTF-1 12 (30%) 22 (55.0%) 6 (15.0%) NapsinA 5 (12.5%) 26 (65,0%) 9 (22.5%) CK5/6 13 (32.5%) 23 (57.5%) 4 (10.0%) P40 8 (20.0%) 31 (77.5%) 1 (2.5%) CD56/Syn/CgA 1 (2.5%) 29 (72.5%) 10 (25%)