CD95 ligand (CD95L) potently induces apoptosis by activating CD95 on t
arget cells. It has recently been reported that melanoma cells in vivo
express a significant amount of CD95L, thereby being immediately able
to kill CD95-bearing immunocompetent cells specific for cancer antige
ns, which infiltrate the lesions. In this study we employed immunohist
ochemistry using an antibody directed against CD95L to investigate at
which stage the melanoma CD95L expression is turned on, Skin biopsies
of 49 lesions from 46 patients were assessed. These included benign an
d dysplastic naevi, melanoma in situ, stage I melanomas (Clark's level
2 or 3). advance-phase melanomas (Clark's level 4 or 5) and lymph nod
e metastases. CD95L was expressed in all of the advance-phase melanoma
s as well as lymph node metastases of cutaneous origin, whereas neithe
r melanoma in situ, benign naevi nor dysplastic naevi reacted positive
ly with the antibody To investigate a link between positivity and tumo
ur size, the data were analysed on the basis of Breslow thickness, and
indicated that expression was observed only when tumours were thicker
than 0.75 mm, We next compared expression of CD95L and HMB-45. CD95L
was positive only in melanomas in a more advanced phase than stage I,
whereas HMB-45 was not only expressed in melanoma cells but also in be
nign pigmented naevi. This indicated the advantage of CD95L staining t
o diagnose melanoma. The present study indicates the significant corre
lation between tumorigenicity and expression of CD95L, and thereby rai
ses the possibility that CD95L may be a useful diagnostic marker for m
alignant melanomas.