Consistency analysis of programmed cell death ligand-1/thyroid transcription factor-1 dual staining in malignant pleural effusion and lung adenocarcinoma histology specimens.

Background: Lung cancer remains the leading cause of cancer-related deaths worldwide, with non-small cell lung cancer (NSCLC) constituting the majority of cases. Immune checkpoint inhibitors have significantly improved outcomes in advanced NSCLC, particularly for patients with programmed cell death ligand-1 (PD-L1) expression. However, obtaining tissue biopsies for PD-L1 assessment in advanced disease is often challenging. Malignant pleural effusion (MPE), frequently associated with advanced lung adenocarcinoma, offers an accessible alternative source for PD-L1 testing. Nevertheless, the reliability of PD-L1 evaluation in cytological specimens from MPE, especially regarding staining methodologies, requires further validation. This study aimed to assess the impact of PD-L1 single staining versus PD-L1/thyroid transcription factor-1 (TTF-1) dual staining on the concordance of PD-L1 tumor proportion scores between paired histologic and cytologic MPE samples. Methods: This retrospective study involved 112 lung adenocarcinoma patients, using paired histological and MPE cytological samples for PD-L1 evaluation via immunohistochemical staining. Tumor proportion score measured PD-L1 levels, withTTF-1 marking lung adenocarcinoma cells. The study compared PD-L1 staining across samples and techniques. Results: This study aimed to evaluate the impact of staining methods on PD-L1 scoring in histological and MPE cytological specimens. The results indicate that the selection of PD-L1 single-stained or PD-L1/TTF-1 dual-stained methodologies within the same sample type did not lead to significant differences in the distribution of PD-L1 tumor proportion scores. However, when evaluating concordance with paired histological specimens, PD-L1/TTF-1 dual staining in MPE cytology samples achieved a significantly higher concordance rate (82.14%) compared to PD-L1 single staining (69.64%), with kappa values increasing from 0.59 to 0.75. Notably, in MPE cytology specimens with low tumor density, PD-L1/TTF-1 dual staining demonstrated a marked advantage over PD-L1 single staining, with the concordance rate of tumor proportion score with histology specimens increasing from 56.86% to 84.31%, with kappa values increasing from 0.47 to 0.78. Conclusions: The application of PD-L1/TTF-1 dual staining in MPE cytological specimens significantly enhances the consistency of PD-L1 expression within tissue specimens, particularly in advanced lung adenocarcinoma patients. This method provides a reliable, evidence-based medical reference that complements histopathological analysis.