<p>Conformance Assessment of PD-L1 Expression Between Primary Tumour and Nodal Metastases in Non-Small-Cell Lung Cancer</p>

Abstract

Introduction: Programmed death-ligand 1 (PD-L1) expression as measured by immunohistochemistry (IHC) has been employed to predict the efficacy of anti-PD-1/PD-L1 therapy. Nevertheless, heterogeneous PD-L1 expression represents a challenge for the selection of patients for anti-PD-1/PD-L1 therapy. Methods: PD-L1 expression using clone 22C3 in 76 resected non-small-cell lung cancer and paired nodal metastases was assessed and classified according to the proportion of immunostained tumour cells using cutoff values of 1%, 5%, and 50%. Results: The concordance rates for PD-L1 expression between primary and metastatic lymph nodes (N1) at these cutoff values were 67.7% (21/31) (Kappa value: 0.455, p<0.000), 60.0% (15/25) (Kappa value: 0.668, p<0.000), and 62.5% (5/8) (Kappa value: 0.497, p<0.000). In 36 paired N1 lymph nodes and N2 lymph nodes, 54.5% (6/11) (Kappa value: 0.625, p<0.000) of cases of PD-L1 expression were coincident at cutoffs of 1%. If stratified by adenocarcinoma and squamous cell carcinoma, 87.5% (14/16) (Kappa value: 0.830, p<0.000) of cases at the 1% cutoff and 46.7% (7/15) (Kappa value: 0.324, p<0.000) of cases at the 1% cutoff were coincident. Conclusion: The results of this study demonstrate that the concordance of PD-L1 expression between primary tumour and nodal metastases is low in non-small-cell lung cancer but is high in adenocarcinoma. Our results also suggest that PD-L1 expression in either lymph nodes or tumour tissues does not predict survival. PD-L1 detection in metastatic lymph nodes is not a suitable replacement for PD-L1 detection in the primary lesion.

PD-L1 expression in non-small cell lung cancer: heterogeneity by pathologic types, tissue sampling and metastasis

“…Metastatic lymph nodes are often used for diagnosis of advanced NSCLC patients. Previous studies have shown that the discrepancy in PD-L1 expression between the primary tumour and matched lymph node metastases in NSCLC is 32.3-71.4% (14,15,36). Our data showed a 28.6% discordance rate between the primary tumour and matched lymph node metastases, which was lower than that reported in previous studies.…”

“…Therefore, sampling error may lead to misclassification of PD-L1 expression status. Some studies have reported on PD-L1 staining regarding intra-tumour heterogeneity in the whole section and small biopsy specimens or intertumour heterogeneity between primary and metastatic tumours (11)(12)(13)(14)(15). However, comprehensive studies on the determination of PD-L1 expression between different materials are still lacking.…”

A PD-L1 Negative Advanced Gastric Cancer Patient With a Long Response to PD-1 Blockade After Failure of Systematic Treatment: A Case Report

“…It would be worthwhile to figure out the reason why the classic prognostic predictors failed in our case and reveal the underlying predictors. In many types of tumors, PD-L1 expression was heterogenous between primary tumours and metastatic lymph nodes, and the expression rate of PD-L1 in the metastasis higher than that of the primary site (2)(3)(4)(5). This discordance is actually exist in gastric cancer as well (6,7).…”

PD‐L1 expression in NSCLC: Role of cell blocks and concordance between samples

“…Kim instead observed higher concordance between the primary and metastatic NCSLC (concordance rate: 75.2%). Intermediate results were found by Xu 24 (concordance rate: 62.5%; k = 0.497) and Luo 25 (concordance rate: 61%; k = 0.39). These intermediate values were similar to those calculated in our series, although we considered only a limited number of cases (50 cases form 25 patients), independently from type, site, and time.…”