Potential involvement of Notch1 signalling in the pathogenesis of primary cutaneous CD30-positive lymphoproliferative disorders.

Abstract

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