Higher concordance of PD‐L1 expression between biopsies and effusions in epithelioid than in nonepithelioid pleural mesothelioma

Abstract

BACKGROUND: Malignant mesothelioma (MM) is a therapy-resistant tumor, often causing an effusion. Drugs targeting the programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) pathway have shown promising results, but assessment of PD-L1 expression to select patients for therapy has mainly been performed on histologic tissue samples. In a previous study, we showed that MM effusions are suitable for PD-L1 assessment with results comparable to those reported in histologic studies, but no studies have compared PD-L1 expression in histologic and cytologic samples. METHODS: PD-L1 expression was determined immunohistochemically (clone 28-8) in 61 paired samples of effusions and biopsies from patients with pleural MM, obtained at the time of diagnosis. Only cases with >100 tumor cells were included. Membranous staining in tumor cells was considered positive at ≥1%, >5%, >10%, and >50% cutoff levels. RESULTS: Of 61 histologic samples, PD-L1 expression was found in 28 and 7 samples at ≥1% and >50% cutoffs, respectively; the corresponding figures for cytology were 21 and 5, respectively. The overall percentage agreement between histology and cytology was 69% and 84%, with a kappa (κ) of 0.36 and 0.08 at ≥1% and >50% cutoffs, respectively. The concordance between cytology and histology tended to be higher for epithelioid MM versus nonepithelioid MM at a ≥1% cutoff. PD-L1 positivity in biopsies, but not in effusions, correlated with the histologic subtype at a ≥1% cutoff. CONCLUSIONS: A moderate concordance of PD-L1 expression between biopsies and effusions from pleural MM, especially for the epithelioid subtype, indicates biological differences between the 2 types of specimens. Cytology and histology may be complementary. Cancer Cytopathol 2021;0:1-11.

Comparison of immunohistochemical mesothelial biomarkers in paired biopsies and effusion cytology cell blocks from pleural mesothelioma

“…Only a few studies have included a limited number of mesotheliomas with paired biopsies and effusion cytology specimens for comparison of protein expression by IHC 17–22 . In a previous study, we showed that IHC assessment of PD‐L1 in paired specimens from pleural mesotheliomas is comparable, but we found a higher concordance between biopsies and effusions in epithelioid than in non‐epithelioid mesotheliomas, 23 which may indicate biological differences. The aim of the present study was to explore the immunoreactivity of eight mesothelioma IHC markers in paired pleural biopsies and pleural fluid cell blocks.…”

“…Preparation of specimens was consistent over time and has previously been described. 23 There were no significant differences in the sampling or preparation methods between hospitals.…”

“…One cell block and one biopsy from each patient were stained with all antibodies included in the present study. Some of the specimens were included in a previous study 23 …”

The Immune Microenvironment of Malignant Pleural Mesothelioma: A Literature Review

“…PD-L1 was found to be less expressed in pleural effusion in comparison with pleural tissues (36% and 46%, respectively, for a PD-L1 ≥ 1%) [106]. Despite lesser expression in cytologic samples, the authors found a moderate concordance in PD-L1 ≥ 1% expression between histologic and cytologic results in the case of epithelioid MPM (Cohen's κ coefficient (95% CI) 0.43 (0.16-0.69)).…”

“…On the contrary, there was no concordance in the case of non-epithelioid MPM. In addition, the concordance in PD-L1 expression between pleural tissues and pleural effusions decreased with the level of cut-off for PD-L1 expression, which highlights intra-tumoral heterogeneity [106].…”