Investigation of epidermotropism in canine mycosis fungoides: Expression of intercellular adhesion molecule-1 (ICAM-1) and beta-2 integrins

In human mycosis fungoides (MF), interactions between LFA-1 (CD11a/CD18) and ICAM-1 (CD54) are involved in lymphocyte adhesion to keratinocytes. The purpose of this study was to evaluate the expression of ICAM-1, beta-2 integrins and class II major histocompatibility complex molecules (MHC II) on keratinocytes and infiltrating lymphocytes in canine MF. Sections of frozen skin biopsy specimens from normal dogs (n=3) and dogs with MF (n=17) were evaluated by immunohistochemistry for expression of ICAM-1, beta-2 integrins, and class II MHC molecules. Our results demonstrated that in canine MF, ICAM-1 was expressed variably on epidermal and follicular keratinocytes. The extent of keratinocyte ICAM-1 expression did not correlate with the degree of lymphocyte epithelial infiltration, nor with lymphocyte LFA-1 expression. This was especially evident in cases of Pagetoid reticulosis-like disease in which prominent lymphocyte epidermotropism was not accompanied by keratinocyte ICAM-1 expression. Keratinocyte class II MHC molecule expression did not correlate with keratinocyte ICAM-1 expression. In conclusion, in canine MF, the lack of statistically significant correlations between epithelial lymphocyte infiltration and keratinocyte ICAM-1 expression, and between keratinocyte ICAM-1 and lymphocyte LFA-1 staining, suggests that the LFA-1/ICAM-1 pathway is not the major adhesion mechanism between lymphocytes and keratinocytes. It is suspected that different ligands of the LFA-1 integrin (e.g. ICAM-2) or other adhesion molecules (e.g. CD2/LFA-3, VLA-1) might be involved in the epitheliotropism phenomenon in canine MF. These hypotheses cannot be evaluated in the dog at this time owing to the lack of specific monoclonal antibodies.