Background:
Impaired regulation of apoptosis is known to be associated with the development of various cancers. fas receptor (apo-1/cd95) binding to its ligand, fas-ligand (fas-l), has been shown to trigger apoptosis in various cell types.
Objectives:
In this study, we examined cd95 and fas-l expression on primary and metastatic melanoma cells from patients to investigate a potential correlation between these measures of apoptosis and different disease stages.
Patients and methods:
Primary melanoma cells were obtained after surgical resection from 19 patients and metastatic cells from fine-needle aspiration of lymph nodes or palpable subcutaneous lesions in 25 patients. normal skin cells were obtained at skin biopsy of 10 healthy donors.
Results:
Flow cytometric analysis revealed that cd95 and fas-l expression was detected in all the kinds of cell studied. in whole cell suspensions, cd95 expression was significantly higher (p < 0.0001) in normal skin cells than in melanoma cells, whatever the stage studied. by contrast, we observed an increase in fas-l expression in melanoma cells compared with normal ones. subsequently, using a double staining method, we studied these measures on hmb45+ cells, a specific marker for melanoma cells, and found that cd95 expression was significantly higher (p = 0.0005) in primary than in metastatic cells while fas-l expression was significantly increased (p = 0. 0004) in metastatic compared with primary cells. furthermore, a relationship was found between cd95 or fas-l expression and breslow thickness; as primary melanoma thickness progressively increased, the percentage of hmb45+ cd95+ cells decreased while that of hmb45+ fas-l+ cells concurrently increased.
Conclusions:
These results suggest that downregulation of cd95 and upregulation of fas-l in melanoma might be considered as concomitant with disease progression.