Expression of Fas and Fas-ligand in primary cutaneous T-cell lymphoma (CTCL): association between lack of Fas expression and aggressive types of CTCL.

Abstract

Fas (CD95; APO-1) is a transmembrane protein that mediates apoptosis upon cross-linking with Fas-ligand (Fas-L). Interaction of Fas-L expressed by cytotoxic T cells with Fas-expressing tumour cells plays an important part in antitumour immune responses. We aimed to investigate Fas and Fas-L expression in frozen and paraffin-embedded material from a large group of patients with cutaneous T-cell lymphoma (CTCL). Immunostaining with monoclonal antibodies against Fas and Fas-L was performed in material from 23 patients with mycosis fungoides (MF), 10 with lymphomatoid papulosis (LyP), 10 with CD30-positive primary cutaneous large T-cell lymphoma (LTCL) and nine with CD30-negative LTCL. The results were correlated with the type and stage of CTCL and clinical features. Expression of Fas by the large majority of the neoplastic T cells was observed in 15 of 15 cases of plaque-stage MF, 10 of 10 cases of LyP and 10 of 10 cases of CD30-positive LTCL, but only in four of 12 cases of tumour-stage MF and two of nine cases of CD30-negative LTCL. In three of four MF patients in whom both plaques and tumours could be studied, a significant decrease in Fas expression was observed with progression from plaque-stage to tumour-stage disease. Fas-L was expressed by > 50% of the neoplastic T cells in 46 of 56 biopsies, and no clear relationship with type of CTCL and clinical behaviour was observed. This study demonstrates loss of Fas expression in aggressive types of CTCL, but not in indolent types of CTCL. These data suggest that loss of Fas receptor expression may be one of the mechanisms that allow tumour cells to escape an effective immune response, and may contribute to the unfavourable prognosis of some types of CTCL.