The initial steps of tumor progression in melanocytic lineage: a histochemical approach

Wollina, U.; Kilian, U.; Henkel, U.; Schaarschmidt, H.; Knopf, B.

Anticancer Research 11(4): 1405-1414


ISSN/ISBN: 0250-7005
PMID: 1746897
Document Number: 772
Antigen expression was studied by immunohistochemistry in 133 human melaonocytic skin lesions to gain insight into the initial steps of tumor development, i.e., in particular the change from melanocytes to benign nevi. We refer to the proposed progression model of Clark and co-workers. The following types of antigens were investigated: (i) intermediate filament antigens (vimentin), (ii) melanoma-associated with antigens (HMB-45, NKI/C-3, MA-930, LS59), (iii) proliferation-associated antigens (S-100, Ki67, Ro/SSA, calmodulin), (iv) progression-associated antigens (HLA-DR, ICAM-I), and (v) basal membrane antigens (bullous pemphigoid antigen, laminin, fibronectin, collagen type IV). The intensity of expression and the topography of immunoreactive pigment cells were compared with the stage of tumor progression. Special attention was paid to the early steps of this process, i.e. the disturbance of the epidermal melanin unit and the development of melanocytic ("nevocellular") nevi. A dramatic shift of antigen expression (antigen types ) between benign and primary malignant melanocyte tumors. So-called dysplastic nevi resembled benign tumors or melanocytes rather than malignant melanoma. Metastatic melanoma of skin showed a relatively high number of Ki67-positive, cycling melanoma cells. The results have a bearing on the concepts of melanocytic nevus ontogenesis and "maturation". It appears that melanocytes lose maturity on their way down to the dermis in contrast to traditional concepts (Abtropfung); this might be of importance for our understanding of melanoma development in association with melanocytic nevi. Our findings are discussed with regard to Clark's model of tumor progression.

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The initial steps of tumor progression in melanocytic lineage: a histochemical approach