Relationship between PD-L1 expression and molecular aberrances in lung adenocarcinoma with solid components

BACKGROUND: Previous studies have evaluated the expression of programmed cell death ligand 1 (PD-L1) in terms of genetic mutation in lung adenocarcinoma (LUAD). However, there are no corresponding large-sample studies in Chinese patients with LUAD with solid components (LUAD-SC). Furthermore, it remains unknown whether the relationship that exists between PD-L1 expression levels and clinicopathological and molecular profiles in small biopsy specimens is consistent with that in surgically-resected specimens. The present study explored the clinicopathological features and genetic correlation of PD-L1 expression in LUAD-SC. METHODS: We collected 1,186 LUAD-SC specimens from Fudan University, Zhongshan Hospital. The tumors were divided into PD-L1 negative, low, and high groups according to the tumor proportion score (TPS)-assessed expression of PD-L1. The mutational information of all specimens was assessed. Each group’s clinicopathological features were also assessed. The relationship between PD-L1 expression levels and clinicopathological features, the overlap with driver genes and the prognostic value were analyzed. RESULTS: In 1,090 resected specimens, a high PD-L1 expression level was more prevalent in the group with predominant SCs, which was remarkably correlated with lymphovascular invasion and a more advanced clinical stage. In addition, the PD-L1 expression level was significantly related to EGFR, KRAS, and BRAF mutations and ROS1 fusions. Meanwhile, in 96 biopsy specimens, the solid-dominant type and EGFR showed a significant difference in PD-L1 expression. Furthermore, compared with their resected counterparts, the biopsy specimens were significantly associated with solid predominant, advanced tumor-node-metastasis (TNM) stage, and high PD-L1 expression. Finally, high PD-L1 expression can be considered a poor prognostic factor for overall survival (OS). CONCLUSIONS: LUAD-SC with high PD-L1 expression levels is linked to unique clinicopathologic characteristics as well as driver mutations. It is important to evaluate the percentage of solid components in both punctured and excised specimens, which may help identify cases of high PD-L1 expression.