title: Heterogeneity of Programmed Cell Death Ligand 1 Expression in Multifocal Lung Cancer.
abstract: The expression of programmed cell death ligand 1 (PD-L1) provides limited predictive value in identifying patients most likely to respond to immunotherapy. As the heterogeneity of PD-L1 expression may lead to sampling error and the misclassification of PD-L1 status, we assessed the distribution of PD-L1 expression in paired, resected multifocal lung cancers.
  
  
  
  PD-L1 was assessed by IHC. Paired lesions were defined as independent primaries or related lesions using mate pair next-generation sequencing. Agreement statistics were used for analysis.
  
  
  
  Sixty-seven multifocal lung cancers from 32 patients were sequenced and stained for PD-L1. There was agreement of PD-L1 expression by the tumor cells in paired lesions of 20 patients and disagreement of PD-L1 expression by the tumor cells in paired lesions of 12 patients (κ = 0.01). Sequencing identified that 23 patients had independent primary lung cancers and that 9 patients had related cancers. In paired lesions of patients with independent cancers, there was agreement of PD-L1 expression by the tumor cells in 12 patients and disagreement in 11 patients (κ = 0.31). In paired lesions of patients with related lung cancers, there was agreement of PD-L1 expression by the tumor cells in 8 patients and disagreement in 1 patient (κ = 0.73).
  
  
  
  The expression of PD-L1 is heterogeneous among paired independent lung cancers, but there are high levels of agreement in intrapulmonary metastasis. Clin Cancer Res; 22(9); 2177-82. ©2015 AACR.
authors.affiliation: Division of Medical Oncology, Mayo Clinic, Rochester, Minnesota. mansfield.aaron@mayo.edu.
authors.forename: Aaron S
authors.initials: AS
authors.lastname: Mansfield
authors.affiliation: Biomarker Discovery Program, Center of Individualized Medicine, Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Murphy
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, Minnesota.
authors.forename: Tobias
authors.initials: T
authors.lastname: Peikert
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Eunhee S
authors.initials: ES
authors.lastname: Yi
authors.affiliation: Biomarker Discovery Program, Center of Individualized Medicine, Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota.
authors.forename: George
authors.initials: G
authors.lastname: Vasmatzis
authors.affiliation: Division of Thoracic Surgery, Mayo Clinic, Rochester, Minnesota.
authors.forename: Dennis A
authors.initials: DA
authors.lastname: Wigle
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Marie Christine
authors.initials: MC
authors.lastname: Aubry
mesh_terms: D000368:Aged; D060890:B7-H1 Antigen / Q000378:metabolism*; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008875:Middle Aged
chemical_list: D060890:B7-H1 Antigen; C423236:CD274 protein, human