title: Heterogeneous expression of PD-L1 in pulmonary squamous cell carcinoma and adenocarcinoma: implications for assessment by small biopsy.
abstract: Predicting response to checkpoint blockade therapy for lung cancer has largely focused on measuring programmed death-ligand 1 (PD-L1) expression on tumor cells. PD-L1 expression is geographically heterogeneous within many tumors, however, and we questioned whether small tissue samples, such as biopsies, might be sufficiently representative of PD-L1 expression for evaluating this marker in lung cancer tumors. To evaluate the extent of variability of PD-L1 expression in small tissue samples, and how that variability affects accuracy of overall assessment of PD-L1 in lung cancer, we scored immunohistochemical staining for PD-L1 in tissue microarray cores from a series of 79 squamous cell lung cancers and 71 pulmonary adenocarcinomas. Our study found substantial inconsistencies for the percentages of cells staining positive for PD-L1 among different tissue microarray cores in many cases of both adenocarcinoma and squamous cell carcinoma. This variable scoring was seen at both high levels and low levels of PD-L1 expression, and by further evaluation of cases with discordant results on full-face sections to assess geographic distribution of staining, we found that discordant results among different tissue microarray cores reflected geographic variation of PD-L1 expression in those tumors. Moreover, we found that as a result of heterogeneous expression, the sensitivity of a single small tissue sample can be as low as 85% for detecting PD-L1 expression at scoring thresholds commonly used in clinical practice. Based on these studies, we conclude that many cases of lung cancer could be inaccurately or variably scored for PD-L1 expression with a single biopsy sample. Accordingly, lung cancer patients can be inconsistently classified for PD-L1 expression status, particularly when a threshold for the percentage of positive cells is used to determine eligibility for checkpoint blockade therapy.
authors.affiliation: The Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Gniadek
authors.affiliation: The Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Qing Kay
authors.initials: QK
authors.lastname: Li
authors.affiliation: The Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Ellen
authors.initials: E
authors.lastname: Tully
authors.affiliation: Russell H Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD, USA.|Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Samit
authors.initials: S
authors.lastname: Chatterjee
authors.affiliation: Russell H Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD, USA.|Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Sridhar
authors.identifier: 0000-0002-6413-7191
authors.initials: S
authors.lastname: Nimmagadda
authors.affiliation: The Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.|Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Edward
authors.initials: E
authors.lastname: Gabrielson
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D060890:B7-H1 Antigen / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism; D001706:Biopsy; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D046888:Tissue Array Analysis
chemical_list: D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor; C423236:CD274 protein, human