Clinicopathological analysis of 110 cases of SMARCA4-deficient conventional non-small cell lung cancer

SMARCA4-deficient conventional non-small cell lung carcinoma (SMARCA4-dNSCLC) is an aggressive NSCLC subtype with significant phenotypic heterogeneity. We retrospectively examined 110 SMARCA4-dNSCLC patients diagnosed between July 2022 and February 2025, focusing on TTF-1 and P40 expression patterns. The median age was 67 years; 91% were male, 58% had smoking history, and 54% presented at stage IV. Adenocarcinoma was predominant (50%) with marked morphologic heterogeneity, and 85% showed complete BRG1 loss. TTF-1 positivity was found in 31% and P40 in 23%; high PD-L1 expression (TPS ≥50%) occurred in 15%. Among 71 tested patients, 19 had at least one driver alteration (total number of alterations was 24). TTF-1-positive tumors were associated with better overall survival (HR = 0.11, 95% CI: 0.01-0.84, P = 0.034), whereas P40 status alone showed no significant association. Cases with TTF-1-/P40+ or TTF-1-/P40- phenotypes showed poorer survival (P = 0.024). SMARCA4-dNSCLC often presented in male smokers with advanced disease and marked heterogeneity. Retained TTF-1 or P40 expression underscores the need to integrate BRG1 status with morphology and lineage markers.