Consistency analysis of PD-L1 expression in NSCLC between pleural effusion and matched primary lung cancer tissues by immunohistochemical double staining.

In clinical practice, PD-L1 detection is prone to nonspecific staining due to the complex cellular composition of pleural effusion smears. In this study, DAB and AEC immunohistochemistry (IHC) 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 (NSCLC) patients, thus, the heterogeneity between metastatic and primary lung cancer was revealed as well. Ninety paired specimens of MPE cell blocks (CBs) and matched primary lung cancer tissues from NSCLC patients were subjected to PD-L1 and TTF-1/p63 IHC double staining. Two experienced pathologists independently evaluated PD-L1 expression using three cutoffs (1%, 10%, 50%). PD-L1 expression in MPE was strongly correlated with that in matched primary lung cancer tissues (R=0.813, P<0.001). Using a 4-tier scale (cutoffs 1%, 10%, 50%), the concordance was 71.1% (Cohen's κ=0.534). Using a 2-tier scale, the concordance was 75.6% (1%, Cohen's κ=0.53), 78.9% (10%, Cohen's κ=0.574) and 95.6% (50%, Cohen's κ=0.754). The rates of PD-L1 positivity in MPE(56.7%) were higher than 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 CBs 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.