Potential involvement of Notch1 signalling in the pathogenesis of primary cutaneous CD30-positive lymphoproliferative disorders.
BACKGROUND
The central role of Notch signalling in T-cell development and oncogenesis raises the question of the importance of this pathway in cutaneous T-cell lymphomas.


OBJECTIVE
To investigate the pattern of expression of Notch and its ligands, Jagged and Delta, in skin samples of primary cutaneous CD30+ lymphoproliferative disorders.


METHODS
Immunohistochemistry of formalin-fixed, paraffin-embedded skin samples from 12 patients with lymphomatoid papulosis (LyP) and 11 patients with primary cutaneous anaplastic large cell lymphoma (ALCL). Immunofluorescence studies of fresh skin samples obtained from three patients with LyP and two patients with primary cutaneous ALCL.


RESULTS
We identified single Notch1-positive cells or small clusters of atypical cells in LyP. Similarly, strongly positive Jagged1 cells tended to be localized in clusters. Primary cutaneous ALCL had higher expression of Notch1 and Jagged1 compared with LyP. Cells expressing Notch1 and Jagged1 were colocalized and a subset of cells expressed both the receptor and the ligand. The expression of the ligand Delta1 was low to undetectable in both types of lymphoproliferations. A subpopulation of lymphoma cells was found to coexpress Notch1 and activated Akt kinase.


CONCLUSIONS
These results imply a potential role for the Notch signalling pathway in the pathogenesis of primary cutaneous CD30+ lymphoproliferative disorders and provide a rationale for the exploration of the activity of Notch antagonists in the therapy of these diseases.
Kamstrup
M R
MR
Department of Dermatology, Bispebjerg Hospital, University of Copenhagen, Bispebjerg Bakke 23, Copenhagen NV, Denmark. mk43@bbh.regionh.dk
Ralfkiaer
E
E
Skovgaard
G L
GL
Gniadecki
R
R
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002135:Calcium-Binding Proteins / Q000302:isolation & purification / Q000378:metabolism*; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000302:isolation & purification / Q000378:metabolism*; D000072100:Jagged-1 Protein; D017730:Ki-1 Antigen / Q000302:isolation & purification / Q000378:metabolism*; D008024:Ligands; D017728:Lymphoma, Large-Cell, Anaplastic / Q000276:immunology* / Q000473:pathology; D017731:Lymphomatoid Papulosis / Q000276:immunology* / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000302:isolation & purification / Q000378:metabolism*; D008875:Middle Aged; D051881:Receptor, Notch1 / Q000302:isolation & purification / Q000378:metabolism*; D000072099:Serrate-Jagged Proteins; D015398:Signal Transduction / Q000276:immunology; D012878:Skin Neoplasms / Q000276:immunology* / Q000473:pathology
D002135:Calcium-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; C000606273:JAG1 protein, human; D000072100:Jagged-1 Protein; D017730:Ki-1 Antigen; D008024:Ligands; D008565:Membrane Proteins; D051881:Receptor, Notch1; D000072099:Serrate-Jagged Proteins