BackgroundImmunotherapies against programmed death ligand-1 (PD-L1) have been established as an effective treatment for a subset of lung cancer patients. Even though it is critical for a successful therapy to know prevalent PD-L1 expression patterns in all affected tissues, information on matching lymph node metastases and immune cells is particularly limited. The purpose of this study was thus to evaluate comparative PD-L1 expression profiles in those tissues.MethodsFDA-approved IHC assays for PD-L1 (Dako 22C3) were performed on a lung tissue array (LC814A, US Biomax) according to manufacturer’s instructions. Histopathological analysis by H-scoring was performed to determine the rate and intensity of positive tumor and immune cell staining for each of the 80 cores. The H score was calculated as follows: A total of up to 300 cells were assessed, per specimen, at 40x high-power magnification (typically over 7–10 fields). A staining level of 0–3 was then assigned to each cell, to designate the intensity of specific positive membranous-to-cytoplasmic staining. The H score was subsequently calculated as% cells staining at level 1 (x1) +% cells staining at level 2 (x2) +% cells staining at level 3 (x3) = total H score per sample. This resulted in a maximum possible H score of 300.ResultsOf the 16 adenocarcinoma tumor samples with a valid staining, 7 (44%) showed positive PD-L1 staining for tumor cells and 10 (63%) for primary immune cells. Importantly, 9 matching metastatic lymph node samples out of the 16 samples (56%) showed an increased PD-L1 H score compared to primary tumors for both tumor cells and immune cells (figure 1). Of the 15 squamous cell carcinoma samples with a valid staining, 11 (73%) showed detectable PD-L1 expression levels in the primary tumor and 12 (80%) in the primary immune cells, while 7 (47%) and 9 (60%) showed lower scores in matching metastatic lymph node tumor cells and their immune cells, respectively (figure 2). Very low or no expression of PD-L1 was detected in small cell lung cancer, as to be expected from previous studies.Abstract 236 Figure 1PD-L1 Staining in adenocarcinomaAbstract 236 Figure 2PD-L1 Staining in squamous cell carcinomaConclusionsSquamous cell carcinomas and adenocarcinomas display significant heterogeneity with regard to PD-L1 expression in associated lymph node metastases. While the reasons for this frequent discordant PD-L1 expression pattern involving both tumor and immune cells need to be investigated further, our findings may help guide the proper interpretation of PD-L1 companion diagnostic test results and subsequent therapeutic decisions.AcknowledgementsThe views in this Abstract have not been formally disseminated by the U.S. Food and Drug Administration and should not be construed to represent any agency determination or policy.
Mutational landscape of paired primary and synchronous metastatic lymph node in chemotherapy naive gallbladder cancer
