The Correlation Among PD ‐ L1 Expression and the Driver Genes Status in Malignant Pleural Effusion of Lung Adenocarcinoma

BACKGROUND: The objective of this study was to investigate the protein expression of PD-L1 in the pleural fluid of lung adenocarcinoma patients with malignant pleural effusion. Additionally, we aimed to analyse the association between PD-L1 expression and the mutational status of ten driver genes: EGFR, ALK, ROS1, BRAF, KRAS, NRAS, HER2, RET, PIK3CA, and MET. METHODS: A total of 161 cytological specimens were collected from patients that had been diagnosed with lung adenocarcinoma at the Fourth Hospital of Hebei Medical University between January 2021 and September 2024. The cytologic samples were tested for tumour PD-L1 expression using a VENTANA PD-L1 (SP263) assay. EGFR, ALK, ROS1, BRAF, KRAS, NRAS, HER2, RET, PIK3CA, and MET mutations in the fresh cytological samples were detected using an amplification refractory mutation system and an ABI 7500 RT-qPCR system. RESULTS: Among 161 pleural fluid cytological specimens, 24.2% (39/161) presented a PD-L1 tumour proportion score (TPS) of ≥ 50%, whereas 39.1% (63/161) presented a TPS ranging from 1% to 49%. Additionally, 36.7% (59/161) demonstrated a TPS of < 1%. The mutation status analysis of 160 pleural fluid cytological specimens revealed EGFR mutations in 75 cases (46.9%), no mutations in 35 cases (21.9%), KRAS mutations in 20 cases (12.5%), ALK mutations in 9 cases, BRAF mutations in 7 cases, MET mutations in 3 cases, ROS1 mutations in another set of 3 cases, and other types of mutations identified in an additional 8 cases. The expression level of PD-L1 in pleural fluid cytological samples from patients with EGFR mutations was not significantly different from that in those from patients with no mutations (p = 0.473). In contrast, the expression levels of PD-L1 in patients with KRAS, ALK, and BRAF mutations were significantly different from those in patients with no mutations (p = 0.045; p = 0.007; p = 0.01). CONCLUSION: Our findings suggest that PD-L1 immunohistochemistry is effective for evaluating pleural fluid cytological specimens and that PD-L1 expression is significantly higher in lung adenocarcinoma patients with malignant pleural effusions associated with the KRAS, ALK and BRAF mutations.