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Basic Sciences

Antigenic Profile of Tumor Progression Stages in Human Melanocytic Nevi and Melanomas

David E. Elder, Ulrich Rodeck, Jan Thurin, Francis Cardillo, Wallace H. Clark, Rosemary Stewart and Meenhard Herlyn
David E. Elder
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Ulrich Rodeck
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Jan Thurin
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Francis Cardillo
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Wallace H. Clark
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Rosemary Stewart
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Meenhard Herlyn
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DOI:  Published September 1989
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Abstract

Sixteen monoclonal antibodies that were obtained after immunization of BALB/c mice with intact melanoma cells or extracts of melanoma cells were tested for reactivity with normal and malignant melanocytic cells in situ, using an immunoperoxidase technique on frozen tissue sections. Sections representing six histopathologically defined stages of tumor progression, ranging from normal melanocytes to highly malignant metastatic lesions, were used. Thirteen monoclonal antibodies (MAbs) did not stain normal melanocytes in situ, whereas three MAbs weakly stained between 1 and 12.5% of melanocytes in 6–22% of the skin sections examined. MAb B 73.1, which was produced by immunization of mice with human natural killer cells and which binds to the Fc receptor of natural killer cells and granulocytes, reacted exclusively with malignant cells that represent the last two stages of tumor progression, vertical growth phase (VGP) primary melanoma and metastatic melanoma. All other antibodies showed variable reactivity with benign proliferative lesions or radial growth phase (RGP), an early stage of primary melanoma. Staining by MAbs that were reactive with gangliosides, unknown antigens, receptors, and two proteins (120/94 kDa protein and 250 kDa glycoprotein) showed a gradual increase in subsequent stages of tumor progression. Two steps in tumor progression were characterized by significant quantitative changes in the expression of antigens detected by the MAbs used in this study. First, mature nevus cells showed significantly higher reactivity with a panel of six MAbs, when compared to normal melanocytes. Second, a separate panel of six MAbs discriminated between RGP and VGP primary melanoma cells. No significant differences in antigen expression were found between dysplastic nevus cells and RGP melanoma, except that some antigens (nerve growth factor receptor and GD2/GD3 gangliosides) appear to be expressed at lower levels in RGP lesions, nor did VGP primary and metastatic melanomas show significant differences in antigen expression. These results suggest that (a) tumor progression of melanocytic cells in vivo is accompanied by significant quantitative differences in the expression of antigens, (b) some of the antigens examined here are associated with biologically aggressive malignant lesions but not normal or premalignant melanocytic cells, and (c) RGP primary melanoma cells are antigenically more similar to nevus cells than to VGP primary melanoma cells.

Footnotes

  • ↵1 Supported by Grants CA-25874, CA-10815, CA-44877, and Ca-25298 from the NIH.

  • ↵2 To whom requests for reprints should be addressed, at The Pigmented Lesion Study Group, Hospital of the University of Pennsylvania, Philadelphia, PA 19104.

  • Received January 5, 1989.
  • Revision received June 6, 1989.
  • Accepted June 14, 1989.
  • ©1989 American Association for Cancer Research.
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September 1989
Volume 49, Issue 18
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Antigenic Profile of Tumor Progression Stages in Human Melanocytic Nevi and Melanomas
David E. Elder, Ulrich Rodeck, Jan Thurin, Francis Cardillo, Wallace H. Clark, Rosemary Stewart and Meenhard Herlyn
Cancer Res September 15 1989 (49) (18) 5091-5096;

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Antigenic Profile of Tumor Progression Stages in Human Melanocytic Nevi and Melanomas
David E. Elder, Ulrich Rodeck, Jan Thurin, Francis Cardillo, Wallace H. Clark, Rosemary Stewart and Meenhard Herlyn
Cancer Res September 15 1989 (49) (18) 5091-5096;
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