Immunohistochemical phenotyping of malignant melanoma. A procedure whose time has come in pathology practice.
Experience has shown that markers created in research laboratories can be adapted to everyday surgical pathology practice for malignant melanomas. These studies are feasible and readily conducted on frozen tissue as is routinely done in typing of lymphoma. The demonstration of heterogeneity using this monoclonal antibody panel, and other antibodies yet to come, may be important for prognostication. Tumor cell heterogeneity of surface antigens reflects disruption of the tumor cell's patterned gene expression. This should be regarded as an indication of different clones of cells (subsets) with a tumor, whether primary or secondary. It is entirely possible that autologous immune cells can kill or at least restrict the growth of subsets of melanoma cells having certain surface antigenic phenotypes while they are incompetent to handle other subsets. This would enable a particular phenotype within a primary melanoma to survive and escape the immunologic regression known to occur in 3 to 6 percent of these tumors. Such patients may present years later with metastases in the brain, liver, gastrointestinal (GI) tract, or lymph nodes. There are also implications in chemotherapy and chemoimmunotherapy for melanoma in this regard. It could be theorized that these agents may dispose of or restrict the growth of some phenotypes, leaving others in a resistant state. Perhaps the MDR gene is activated. Alternatively a tumor suppressor gene(s) could be absent or inactivated, as in neuroblastoma and carcinoma of the breast and lung. Markers present at the cell membrane surfaces and in the membranes themselves constitute an important field for study in the understanding of tumorigenesis. Many of these markers are present in embryos as early as the 4-to-8-cell stage and in blastocysts. Embryonic antigens in the intercell mass of blastocysts are stage-specific embryonic antigens. They are signals for organ development and the differentiation of cells. At various stages of this development, these markers disappear, especially upon differentiation into tissue types and specific organs. These cell signals are therefore organogenesis markers. Detecting a given antigen is not simple because it may be present but not immunohistochemically detectable because glycosylation, acetylation, phosphorylation, or sulfation have not taken place, or have resulted in a structural conformation not recognized by monoclonal antibodies.(ABSTRACT TRUNCATED AT 400 WORDS)
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Duray
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Ernstoff
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Titus-Ernstoff
D000951:Antigens, Neoplasm; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods*; D008545:Melanoma / Q000235:genetics* / Q000378:metabolism; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins / Q000378:metabolism; D010641:Phenotype
D000951:Antigens, Neoplasm; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins