Consistency Analysis of PD-L1 Expression in NSCLC Between Pleural Effusion and Matched Primary Lung Cancer Tissues by Immunohistochemical Double Staining

In clinical practice, programmed death ligand 1 (PD -L1) detection is prone to nonspecific staining due to the complex cellular composition of pleural effusion smears. In this study, diaminobenzidine (DAB) and 3-amino-9-ethylcarbazole (AEC) immunohistochemistry double staining was performed to investigate PD -L1 expression in tumor cells from malignant pleural effusion (MPE). MPE was considered as a metastasis in non-small cell lung cancer patients; thus, the heterogeneity between metastatic and primary lung cancer was revealed as well. Ninety paired specimens of MPE cell blocks and matched primary lung cancer tissues from non-small cell lung cancer patients were subjected to PD -L1 and thyroid transcription factor-1(TTF-1)/p63 immunohistochemistry double staining. Two experienced pathologists independently evaluated PD -L1 expression using 3 cutoffs (1%, 10%, and 50%). PD -L1 expression in MPE was strongly correlated with that in matched primary lung cancer tissues (R = 0.813; P < .001). Using a 4-tier scale (cutoffs: 1%, 10%, and 50%), the concordance was 71.1% (Cohen's K = .534). Using a 2-tier scale, the concordance was 75.6% (1%, Cohen's K = 0.53), 78.9% (10%, Cohen's K = 0.574), and 95.6% (50%, Cohen's K = 0.754). The rates of PD -L1 positivity in MPE (56.7%) were higher than that in lung tissues (32.2%). All 27 discordant cases had higher scores in MPE. The double-staining method provided superior identification of PD -L1 -positive tumor cells on a background with nonspecific staining. In conclusion, PD -L1 expression was moderately concordant between metastatic MPE cell blocks and matched primary lung carcinoma tissues, with variability related to tumor heterogeneity. MPE should be considered to detect PD -L1 when histological specimens are unattainable, especially when PD -L1 expression is >50%. PD -L1 positivity rates were higher in MPE. Double staining can improve PD -L1 detection by reducing false-negative/positive results. (c) 2024 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.