Interobserver agreement in programmed cell death‐ligand 1 immunohistochemistry scoring in nonsmall cell lung carcinoma cytologic specimens

Abstract

BackgroundThe evaluation of PD‐L1 expression in nonsmall cell lung carcinoma (NSCLC) is becoming increasingly important given the effectiveness of PD‐L1 inhibitors. Although cytologic specimens have been shown to be compatible with surgical specimens to evaluate PD‐L1 immunohistochemistry (IHC), evidence of the reproducibility of PD‐L1 in cytologic specimens is lacking. The aim of this study is to evaluate interobserver agreement in PD‐L1 IHC in cytologic specimens.MethodsPD‐L1 IHC was performed on 86 NSCLC cytology specimens using Dako PD‐L1 IHC 22C3 pharmDx. The digitally scanned whole slide images (WSI) were read by five pathologists. Each case was given a Tumor Proportion Score (TPS) and the results were compared between the observers. The interobserver concordance was assessed using 1% and 50% as cutoffs.ResultsTPSs were highly correlated among observers (Spearman correlation coefficient, 0.86‐0.94). Using greater than 1% as a cutoff, interobserver agreement measured by Fleiss Kappa was 0.74 for all pathologists and Cohen's Kappa coefficient ranged from 0.49 to 0.83, consistent with moderate to substantial agreement. With a cutoff of greater than 50%, Fleiss Kappa was 0.79 for all pathologists and the kappa values ranged from 0.63 to 0.90, consistent with substantial to almost perfect agreement. Several pitfalls were identified by reviewing discordant cases, including staining in macrophages, stromal cells, and intratumoral heterogeneity.ConclusionOur data suggest that TPS of PD‐L1 IHC on cytology specimens is reproducible, with a better agreement when using 50% as the cutoff value. However, special attention is required when the TPS is near the 1% cutoff.

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

“…Another factor is potential difficulty in evaluating cytology, and the Blueprint 2 study reported a clearly higher interobserver variability for cytology than for histology [41], but a moderate to near perfect interobserver agreement for cytological samples has been reported in other investigations [42][43][44]. In our experience, interobserver discordance is not higher for PE than other cytological specimens, but it may be discussed if training in PD-L1 evaluation specifically on cytological cases is needed.…”

PD‐L1 and beyond: Immuno‐oncology in cytopathology

“…Consistently, the Blueprint (BP) PD‐L1 Immunohistochemistry Comparability Project phase 2 6 reported a good ICC at all cutoff levels (k equal to 0.60‐0.80), for both glass (0.78) and digital (0.85) slides among 24 pathologists who analyzed 22 CBs. More recently, quite similar interobserver agreement rates were reported by Sinclair et al 55 (k equal to 0.74) and Kravsotv et al 43 (k equal to 0.66) (Table 3). Despite such encouraging agreement rates, some studies have highlighted the fact that that variability among observers is generally more pronounced in cytological samples than in biopsies and surgical specimens, 6,56 suggesting that the interpretation of PD‐L1 in cytological samples is more challenging.…”

EMMPRIN expression is associated with metastatic progression in osteosarcoma

“…[ 23 ] To study the role of EMMPRIN in tumor-stromal interaction, we co-cultured SaOS-2 cells with osteoblasts (hFOB). Co-culturing of osteoblasts and SaOS-2 enhanced the stimulation of pro-MMP2.…”

“…In line with our study, Zhou et al reported that expression of EMMPRIN was detected in 70% of patients with osteosarcoma. EMMRPIN levels were elevated in ostesarcoma patients with advanced disease and worse response to chemotherapy as compared to those with less advanced stage and better response to chemotherapy [ 23 ]. Variable expression of EMMPRIN was found in 65% of human prostate cancer tissues and correlated significantly with progression parameters [ 24 ].…”

“…After finding the areas showing the most tumor cells at × 40 magnificatio, cells were counted under × 100 magnification. Samples were graded into high and low expression groups by the percentage of positively staining cells among tumor cells with a cutoff value of 50% [ 23 ]. Examination of the histological sections was performed using Nikon Eclipse Ci microscope (Nikon Corp., Tokyo, Japan) and the automatic exposure and iSolution Lite software for microscopic images.…”