Novel markers of normal and neoplastic human plasmacytoid dendritic cells.
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.
Marafioti
Teresa
T
Leukaemia Research Fund Immunodiagnostics Unit, Nuffield Department of Clinical Laboratory Sciences, John Radcliffe Hospital, Oxford, UK. teresa.marafioti@ndcls.ox.ac.uk
Paterson
Jennifer C
JC
Ballabio
Erica
E
Reichard
Kaaren K
KK
Tedoldi
Sara
S
Hollowood
Kevin
K
Dictor
Michael
M
Hansmann
Martin-Leo
ML
Pileri
Stefano A
SA
Dyer
Martin J
MJ
Sozzani
Silvano
S
Dikic
Ivan
I
Shaw
Andrey S
AS
Petrella
Tony
T
Stein
Harald
H
Isaacson
Peter G
PG
Facchetti
Fabio
F
Mason
David Y
DY
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
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