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Title: Canine cutaneous histiocytoma : characterisation of a dendritic cell tumour
Author: Baines, S. J.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2002
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Canine cutaneous histiocytoma (CCH) is a common, benign tumour of dendritic cells (DCs). This tumour undergoes an early period of rapid growth over one to four weeks, followed by spontaneous regression, in most cases, over the next one to three months. Regression is associated with the influx of CD8+ T lymphocytes. The research in this thesis aimed to identify the state of differentiation of the neoplastic cells and to identify if they matched DC parameters on the basis of morphology, phenotype and function. Neoplastic dendritic cells isolated from excised tumours had a monocytoid appearance on light microscopy. On electron microscopy, the predominant cell morphology was monocytoid, but a greater proportion of cells with dendritic morphology were seen in lesions undergoing regression. Flow cytometry analysis of CCH cells revealed expression of CD1a, CD1c, CD11a, CD11c, CD18, CD45, CD45R, MHC-I, MHC-II and E-cadherin, confirming their Langerhans cell origin. In addition, the cells also showed uniform expression of CD1b, and expressed CD11b, CD44, CD49d and ICAM-I, consistent with an activated phenotype. CCH cells isolated from lesions undergoing regression had a higher level of expression of MHC-I, MHC-II and ICAM-1 compared with those cells isolated from early lesions. Immunohistochemical staining for MHC-II revealed that tumour cells from the early stage showed predominantly focal juxtanuclear staining, whereas those from regressing lesions showed mainly diffuse cytoplasmic staining. This is consistent with the hypothesis that CCH cells isolated from lesions in the early proliferative phase represent immature dendritic cells and CCH cells isolated from lesions in the regressing phase represent mature DCs. The CCH cells induced a strong proliferative response to the allogenic and autologous mixed lymphocyte reaction, consistent with their dendritic cell origin. When compared according to clinical stage of the lesion, CCH cells isolated from later lesions resulted in a greater proliferative response for a given number of stimulator cells than CCH cells isolated from early lesions. CCH cells exhibited a high rate of macropinocytosis as expected for cells of the myeloid/dendritic lineage. CCH cells from later lesions showed a significantly higher rate of macropinocytosis than those from early lesions. Macropinocytosis was down-regulated on culture of the cells.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available