IMMUNOPHENOTYPICALLY VARIED CELL SUBPOPULATIONS IN PRIMARY AND METASTATIC HUMAN MELANOMAS, MONOCLONAL-ANTIBODIES FOR DIAGNOSIS, DETECTION OF NEOPLASTIC PROGRESSION AND RECEPTOR DIRECTED IMMUNOTHERAPY

During a systematic, immunocytochemical screening of 40 human cutaneou s melanomas (30 primary and 10 metastatic) for immunophenotype (IP) he terogeneity, we employed a library of 20 well characterized commercial ly available mono- and polyclonal antibodies. The use of the sensitive , indirect, four to six step immunoperoxidase or alkaline phosphatase conjugated streptavidin-biotin antigen detection technique provided ex cellent results. The immunocytochemically most characteristic IP for p rimary cutaneous melanoma, as detected by us was: NMB45(+), S-100(+), CEA(+), vimentin(+), cytokeratin 19(+), p53(+), Rbgene(+), nm23(+), HL A-DR(+), HLA-DP+, c-erbB3/HER-3(+/-); cytokeratin 10/13(+/-) , HLA-DQ( -), cytokeratin 5/8(-), EMA(-). c-myc(-) and actin(-). During melanoma progression, a tendency toward poor differentiation (dedifferentiatio n) and an increase in c-myc expression have both been observed the lat ter downregulating HLA-A,B,C expression and consequently diminishing t he possibility of melanoma cell lysis by powerful CD8(+), cytotoxic T lymphocytes (CTL) of other cytotoxic cells which requires HLA class I antigens. The development of the metastatic potential in melanomas cau sed an increase in CEA expression, eliminated the presence of nm23, an d prompted the appearance of actin among the intermediate filaments, c omposing the cytoskeleton of these malignant tumor cells. The most cha racteristic IP for MMs, identified by this study was: HMB45(+), S-100( +), CEA(+), EMA(+), vimentin(+), HLA-DR(+), HLA-DP+, cytokeratin 19(+) , actin(-), c-erbB3/HER-3(+), p53(+), cytokeratin 10/13(+/-), c-myc(+/ -), c-erbB2/HER-2(+/-), HLA-DQ(-), cytokeratin 5/8(-), Rb gene(-), nm2 3(-). It has been observed that adhesion molecules and integrins play a significant role in the complex process of melanoma metastasis and t hus we propose a blocking of these de novo expressed molecules with th e appropriate antibodies as a form of immunotherapy of PMs and early s tages of MMs.