Expression of programmed cell death ligand 1 in non–small cell lung cancer: Comparison between cytologic smears, core biopsies, and whole sections using the SP263 assay

Abstract

Background Evaluation of programmed cell death ligand 1 (PD‐L1) expression can be made on both resection specimens and diagnostic biopsies; however, more than 30% of patients with advanced non–small cell lung cancer (NSCLC) do not have adequate histologic material to perform PD‐L1 assays and require additional biopsies. In addition, in our practice, more than 16% of cases have cytological smears as the only available material. Our aim was to validate the PD‐L1 immunocytochemistry assay on cytological smears and compare its accuracy with the results obtained from tissue cores and whole tumor sections using the clinically relevant cutoff of 50%. Method We compared the PD‐L1 staining results of cytological smears to those from tissue cores or whole sections in 50 and 53 NSCLC cases, respectively, using the SP263 assay after scanning hematoxylin and eosin slides. Results We found an overall agreement of 90.6% between cytological smears and whole sections; specifically, we found absolute concordance between smears with PD‐L1 expressed in <10% and ≥50% of cells and whole sections with PD‐L1 expressed in <50% and ≥50% of cells, respectively. In addition, slightly lower diagnostic accuracy was found for the cytological smears in comparison with the tissue cores, but the difference was not statistically significant. We found excellent intraobserver and good interobserver agreement in the evaluation of PD‐L1 on smears. Conclusion Immunocytochemistry on cytological smears is a reliable method for determination of PD‐L1 at the 50% cutoff when positive cells are <10% or ≥50%; for cases showing PD‐L1 expression in 10% to 49% of cells, additional tissue sampling may be necessary.

Utility of PD‐L1 immunocytochemistry using body‐fluid cell blocks in patients with non‐small‐cell lung cancer

“…The ICC and IHC scores highly correlated (Pearson's correlation coefficient .804), indicating that exudate samples are a viable alternative to tissue samples for PD‐L1 immunostaining. We used three PD‐L1 expression cutoffs reported previously . The overall concordance rates using cutoffs of 1%, 10%, and 50% were similar.…”

“…The concordance of PD‐L1 positivity between clinical specimens varied depending on the cutoffs used and the underlying clinicopathological features. One study suggested that the cytological smear results are reliable when the PD‐L1 positive rate is <10% or ≥50%, and additional histological confirmation may be necessary when the PD‐L1 expression is 10%‐49% . One study that included cytology specimens with low cellularity showed that among cell blocks with fewer than 100 cells, low concordance was observed with the corresponding surgical specimens (κ = 0.19) .…”

“…The PD‐L1 scores of matched IHC and ICC specimens were compared as a continuous variable to assess the strength of correlation. Next, the specimens were divided into subgroups for further analyses using cutoffs of 1%, 10%, and 50% …”

Adequate tumour cellularity is essential for accurate PD‐L1 immunohistochemistry assessment on cytology cell‐block specimens

“…In this study we have demonstrated substantial agreement between or liquid-based cytology slides appears less concordant with subsequent biopsy specimens. 15,[19][20][21] Bulk comparisons (ie, non-paired samples) appear to show slightly higher PD-L1 expression in cytology specimens, of uncertain significance. 22,23 PD-L1 IHC on histology specimens is acknowledged to be an imperfect biomarker and ultimately the ability of a test to predict responses to anti-PD-1 immunotherapy is the most appropriate standard against which to compare new tests or test conditions.…”

“…A number of previous studies have investigated the potential usefulness of cytology specimens in PD‐L1 IHC assessment in NSCLC, reviewed in Hernandez et al; however, the range of different assays, staining platforms, scoring systems and reported statistics makes comparison across studies difficult. In general, studies of paired histology and cell‐block specimens have shown acceptable concordance, while direct IHC performed on smears or liquid‐based cytology slides appears less concordant with subsequent biopsy specimens . Bulk comparisons (ie, non‐paired samples) appear to show slightly higher PD‐L1 expression in cytology specimens, of uncertain significance …”