title: Expression of programmed cell death 1 ligand 2 (PD-L2) is a distinguishing feature of primary mediastinal (thymic) large B-cell lymphoma and associated with PDCD1LG2 copy gain.
abstract: Primary mediastinal (thymic) large B-cell lymphoma (PMBL) and diffuse large B-cell lymphoma (DLBCL) are tumors with distinct clinical and molecular characteristics that are difficult to distinguish by histopathologic and phenotypic analyses alone. Programmed cell death 1 ligand 2 (PD-L2) is a cell surface protein expressed by activated macrophages and dendritic cells that binds PD-1 on T cells to inhibit immune responses. Amplification and/or translocations involving chromosome 9p24.1, a region that includes PDCD1LG2-encoding PD-L2, is a common event in PMBL but not DLBCL and suggests that PD-L2 expression might be a distinguishing feature of PMBL. We developed an assay for the immunohistochemical detection of PD-L2 protein in fixed biopsy specimens (PD-L2 IHC), which we applied to a cohort of PMBLs and DLBCLs. For a subset of cases, we correlated the results of PD-L2 IHC with PDCD1LG2 copy number (CN) as determined by quantitative polymerase chain reaction. Twenty-three of 32 (72%) PMBLs but only 1 of 37 (3%) DLBCLs were positive by PD-L2 IHC. Among PMBLs with PDCD1LG2 CN gain, all were positive by PD-L2 IHC. One PMBL without CN gain was positive by PD-L2 IHC. When expressed in PMBL, PD-L2 was restricted to tumor cells and not detected on intratumoral macrophages. We conclude that PD-L2 protein is robustly expressed by the majority of PMBLs but only rare DLBCLs and often associated with PDCD1LG2 copy gain. PD-L2 IHC may serve as a useful ancillary test for distinguishing PMBL from DLBCL and for the rational selection of patients for therapeutic antibodies that inhibit PD-1 signaling.
authors.affiliation: *Department of Pathology, Brigham & Women's Hospital †Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.
authors.forename: Min
authors.initials: M
authors.lastname: Shi
authors.forename: Margaretha G M
authors.initials: MG
authors.lastname: Roemer
authors.forename: Bjoern
authors.initials: B
authors.lastname: Chapuy
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Liao
authors.forename: Heather
authors.initials: H
authors.lastname: Sun
authors.forename: Geraldine S
authors.initials: GS
authors.lastname: Pinkus
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Shipp
authors.forename: Gordon J
authors.initials: GJ
authors.lastname: Freeman
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Rodig
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D003937:Diagnosis, Differential; D005784:Gene Amplification; D018628:Gene Dosage; D006801:Humans; D007150:Immunohistochemistry; D016393:Lymphoma, B-Cell / Q000175:diagnosis*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000175:diagnosis*; D008479:Mediastinal Neoplasms / Q000175:diagnosis*; D016133:Polymerase Chain Reaction; D061027:Programmed Cell Death 1 Ligand 2 Protein / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; C556977:PDCD1LG2 protein, human; D061027:Programmed Cell Death 1 Ligand 2 Protein