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S-100 protein is a low molecular weight soluble protein first isolated from the brain and initially believed to be exclusively a glial marker. Two subunits of S-100 protein have been identified, and they are differently expressed by various cells. The beta subunit is present in all S-100 positive cells and tumors. In contrast, the alpha subunit is detectable only in neurons and lymph node macrophages. The S-100 protein is a fairly stable antigen that withstands formalin fixation and paraffin embedding. Consequently, the presence of S-100 protein is readily demonstrated in routinely processed malignant melanomas. S-100 protein has been found in normal melanocytes, langerhans cells, histiocytes, chondrocytes, lipocytes, skeletal and cardiac muscle, schwann cells, epithelial and myoepithelial cells of the breast, salivary and sweat glands, in addition to glial cells. Neoplasms derived from these cells also express S-100 protein to varying degrees. A large proportion of well-differentiated tumors of salivary gland, adipose, cartilaginous tissue, and schwann cell derived tumors express S-100 protein.