title: Novel markers of normal and neoplastic human plasmacytoid dendritic cells.
abstract: Plasmacytoid dendritic cells (pDCs) are involved in innate immunity (eg, by secreting interferons) and also give rise to CD4+CD56+ hematodermic neoplasms. We report extensive characterization of human pDCs in routine tissue samples, documenting the expression of 19 immunohistologic markers, including signaling molecules (eg, BLNK), transcription factors (eg, ICSBP/IRF8 and PU.1), and Toll-like receptors (TLR7, TLR9). Many of these molecules are expressed in other cell types (principally B cells), but the adaptor protein CD2AP was essentially restricted to pDCs, and is therefore a novel immunohistologic marker for use in tissue biopsies. We found little evidence for activation-associated morphologic or phenotypic changes in conditions where pDCs are greatly increased (eg, Kikuchi disease). Most of the molecules were retained in the majority of pDC neoplasms, and 3 (BCL11A, CD2AP, and ICSBP/IRF8) were also commonly negative in leukemia cutis (acute myeloid leukemia in the skin), a tumor that may mimic pDC neoplasia. In summary, we have documented a range of molecules (notably those associated with B cells) expressed by pDCs in tissues and peripheral blood (where pDCs were detectable in cytospins at a frequency of <1% of mononuclear cells) and also defined potential new markers (in particular CD2AP) for the diagnosis of pDC tumors.
authors.affiliation: Leukaemia Research Fund Immunodiagnostics Unit, Nuffield Department of Clinical Laboratory Sciences, John Radcliffe Hospital, Oxford, UK. teresa.marafioti@ndcls.ox.ac.uk
authors.forename: Teresa
authors.initials: T
authors.lastname: Marafioti
authors.forename: Jennifer C
authors.initials: JC
authors.lastname: Paterson
authors.forename: Erica
authors.initials: E
authors.lastname: Ballabio
authors.forename: Kaaren K
authors.initials: KK
authors.lastname: Reichard
authors.forename: Sara
authors.initials: S
authors.lastname: Tedoldi
authors.forename: Kevin
authors.initials: K
authors.lastname: Hollowood
authors.forename: Michael
authors.initials: M
authors.lastname: Dictor
authors.forename: Martin-Leo
authors.initials: ML
authors.lastname: Hansmann
authors.forename: Stefano A
authors.initials: SA
authors.lastname: Pileri
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Dyer
authors.forename: Silvano
authors.initials: S
authors.lastname: Sozzani
authors.forename: Ivan
authors.initials: I
authors.lastname: Dikic
authors.forename: Andrey S
authors.initials: AS
authors.lastname: Shaw
authors.forename: Tony
authors.initials: T
authors.lastname: Petrella
authors.forename: Harald
authors.initials: H
authors.lastname: Stein
authors.forename: Peter G
authors.initials: PG
authors.lastname: Isaacson
authors.forename: Fabio
authors.initials: F
authors.lastname: Facchetti
authors.forename: David Y
authors.initials: DY
authors.lastname: Mason
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001706:Biopsy; D002352:Carrier Proteins / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism; D003713:Dendritic Cells / Q000378:metabolism* / Q000473:pathology; D003937:Diagnosis, Differential; D005260:Female; D019337:Hematologic Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D050835:Interferon Regulatory Factors / Q000378:metabolism; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D054219:Neoplasms, Plasma Cell / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D009687:Nuclear Proteins / Q000378:metabolism; D010950:Plasma Cells / Q000378:metabolism* / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D012097:Repressor Proteins; D012878:Skin Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D051199:Toll-Like Receptor 7 / Q000378:metabolism; D051217:Toll-Like Receptor 9 / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism; D000099185:Interferon Regulatory Factor-8; D000099232:Proto-Oncogene Protein Spi-1
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D050835:Interferon Regulatory Factors; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D051199:Toll-Like Receptor 7; D051217:Toll-Like Receptor 9; D015534:Trans-Activators; D000099185:Interferon Regulatory Factor-8; D000099232:Proto-Oncogene Protein Spi-1; C113939:B cell linker protein; C486563:BCL11A protein, human; C114545:CD2-associated protein; C495348:TLR7 protein, human; C495371:TLR9 protein, human