TAP1 down-regulation in primary melanoma lesions: An independent marker ofpoor prognosis

Melanoma tumor thickness is a major prognostic factor. Thin lesions, howeve r, may metastasize, and sometimes thick tumors may not. To investigate the role of HLA class 1-mediated antigen presentation, we correlated the expres sion of components of the antigen-processing machinery in primary melanoma lesions with their thickness and with the development of metastases. Sevent een formalin-fixed, par affin-embedded primary melanomas thinner than 0.76 mm and 21 thicker than 1.50 mm were stained with anti-LMP2, -LMP7, -TAP1, - TAP2, -HLA class 1 and -beta (2)-microglobulin monoclonal antibodies. Twent y patients remained tumor-free in the follow-up period (10.5 +/- 1.8 years) . Eighteen patients relapsed within a median period of 15.0 months followin g tumor excision, Expression of all markers in the tested lesions was down- regulated, the frequency ranging: from about 40% for LMP and TAP subunits t o about 70% for HLA class 1 antigens, Expression of all markers was not: co rrelated with tumor thickness. Only TAP1 and TAP2 down-regulation was signi ficantly (p = 0.026 and 0.0425 respectively) correlated with the developmen t of metastases. This correlation was independent of tumor thickness for TA P 1,We suggest that TAP 1 and probably TAP2 expression in primary lesions r epresents an independent prognostic marker in melanoma, Abnormalities in an tigen presentation may account for the lack of absolute correlation between tumor thickness and prognosis. (C) 2001 Wiley-Liss, Inc.