Cytology cell blocks from malignant pleural effusion are good candidates for PD-L1 detection in advanced NSCLC compared with matched histology samples

Abstract

Background: Detection of programmed cell death ligand-1 (PD-L1) by immunohistochemistry (IHC) has been commonly used to predict the efficacy of treatment with PD-1/PD-L1 inhibitors. However, there is limited literature regarding the reliability of PD-L1 testing using malignant pleural effusion (MPE) cell blocks. Here, we assess PD-L1 expression in sections from MPE cell blocks and evaluate the value of IHC double staining in the interpretation of PD-L1 expression. Methods: In all, 124 paired formalin-fixed tissues from advanced NSCLC patients, including MPE cell blocks and matched histology samples, were included. PD-L1 expression was assessed using the SP263 assay, and the tumor proportion score (TPS) and the staining intensity were evaluated. PD-L1 staining results were also compared between IHC double and single staining techniques. Results: PD-L1 expression was concordant in most paired cases (86/101, 85.1%) among three TPS cutoffs (<1%, 1-49% and ≥ 50%), with a kappa value of 0.774. Moreover, a significant difference in PD-L1 expression between MPE cell blocks and biopsy samples was observed (p = 0.005). For the 15 discordant pairs, 13 MPE cell block samples showed increased expression of PD-L1. Compared with the standard IHC single PD-L1 assay, double staining with anti-TTF-1 and anti-PD-L1 revealed a negative effect on PD-L1 expression testing and resulted in weaker staining intensity and a lower TPS (p = 0.000). Conclusions: MPE cell block samples are good candidates for PD-L1 expression detection in advanced NSCLC patients. The mechanism and clinical significance of the higher PD-L1 expression rate in MPE cell blocks compared with small biopsy samples remain to be evaluated prospectively.

Factors Influencing Concordance of PD-L1 Expression between Biopsies and Cytological Specimens in Non-Small Cell Lung Cancer

“…The lower PD-L1 concordance seen for our PE cytology, which is in contrast with some studies [32,33], may be attributed to one or more several factors. The PE samples represent metastases while all biopsies in our cohort were from the primary tumour.…”

“…The studies by Grosu et al [32] and Zou et al [33] reported a rather high PD-L1 concordance between histological specimens and PE cell blocks, with weighted κ values of 0.76 and 0.77, respectively, for PD-L1 <1% vs. 1-49% vs. ≥50% (the corresponding weighted κ was 0.25 in our PE subgroup). One obvious difference compared to our study is the mixture of biopsies and resections as histological specimens in these studies.…”

Programmed death‐ligand 1 (PD‐L1)/thyroid transcription factor‐1 double immunohistochemical staining facilitates scoring of tumor PD‐L1 expression in cytopathology specimens from lung adenocarcinoma patients

“…Our finding indicated that only 3 out of 84 samples show true difference in PD‐L1 staining between single staining and double staining in either cytopathology or histopathology specimens, all of them showing staining accentuation in double staining. This is in contrast to the results reported by Zou et al, 16 who claimed that double‐staining with TTF‐1 resulted in a “general decrease” of PD‐L1 staining in tumor cells. Important differences between the current study and the Zou et al study include the anti–TTF‐1 antibody used (clone SP141 vs clone SPT24, respectively), difference in staining protocol, and absence of a cytotechnologist double‐check in the study by Zou et al More research from different laboratories is required to clarify this important issue.…”

PD-L1 Testing in Cytological Non-Small Cell Lung Cancer Specimens: A Comparison with Biopsies and Review of the Literature

“…Grosu et al [50] and Zou et al [57] showed a higher concordance for PD-L1 in pleural effusions compared to matched histological samples (87–97% at 1% cutoff) than did Yoshimura et al [37] and Jug et al [58] for EBUS-guided samples (70–84%). Such a trend is not seen when comparing our 2 cohorts but may be concealed by other differences with greater impact.…”