The human immune repertoire appears to be capable of recognizing norma
l antigens expressed by tumor cells. Among these antigens, those of di
fferentiation, characterized by a restricted tissue expression, could
be of clinical interest since they may represent a target for immunoth
erapeutic protocols. In this context we have evaluated, in benign and
malignant lesions of the melanocytic lineage, the expression of the Me
lan-A/MART-1 antigen, which has been shown to be recognized by T cells
, of HLA-A2 melanoma patients. The immunohistochemical analysis conduc
ted with a Melan-A/MART-1 monoclonal antibody demonstrated that the an
tigen expression does not correlate with transformation or tumor progr
ession. At variable levels Melan-A/MART-1, differently from other diff
erentiation antigens, is homogeneously expressed by multiple autologou
s metastases and by melanoma metastases at different body sites. This
tissue distribution adds further biological support to the ongoing use
of Melan-A/MART-1-related peptides in active immunotherapy.