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

BACKGROUND: 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. OBJECTIVES: 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). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Expression of Fas and Fas ligand in cutaneous B-cell lymphomas.

Primary cutaneous B-cell lymphomas (CBCLs) represent a rare, but distinct group of B-cell neoplasms with a different clinical behaviour to B-cell lymphomas secondarily involving the skin. Fas-Fas ligand (Fasl) expression was investigated in a group of primary and secondary CBCLs to gain an insight into the putative role of these apoptotic molecules in the clinical behaviour of these lymphomas. Frozen and paraffin sections from 32 patients with a CBCL were investigated for Fas and Fasl expression, using immunohistochemistry. This group included 24 primary CBCLs [14 primary cutaneous follicle centre cell lymphomas (PCFCCLs), six primary cutaneous large B-cell lymphomas (PCLBCLs) on the leg, and four primary cutaneous immunocytomas] and eight secondary CBCLs. The results were correlated with follow-up data, bcl-2, and ICAM-1 expression. High Fas expression and absent or low Fasl expression were detected in the vast majority of PCFCCLs and immunocytomas. The group of PCLBCLs on the leg, which have an intermediate prognosis, showed variable results with relatively higher Fasl expression. The highest Fasl expression was found in the more aggressive secondary CBCLs whereas in this group, Fas was undetectable in five of eight cases. Statistical analysis showed that Fas and ICAM-1 expression was strongly related to a favourable prognosis, whereas expression of Fasl and bcl-2 was related to a very poor prognosis. Although only type of CBCL and age, but not Fas, Fasl, bcl-2, and ICAM-1 expression, proved independent prognostic parameters using multivariate analysis, the results of this study suggest that differences in the expression of Fas and Fasl, as well as bcl-2 and ICAM-1, contribute to the differences in clinical behaviour between these different types of CBCL.