S-100 is a marker that is most commonly used to identify cells of neural origin, including melanocytes and melanoma.  S-100 is an antibody to the calcium-flux determinant protein, which is expressed by many different tissue types including: melanocytes, Schwann cells (nerve fibers), neural elements (astrocytes, ependyma, and oligodendroglia), Langerhans histiocytes, myoepithelial cells, reticulum cells, and salivary gland.  Unfortunately, this variability of specificity can make the use of the S-100 antibody in isolation “risky business.”  In fact, some carcinomas may express S-100.  Therefore, in the work-up of a poorly differentiated lesion, it should be part of a larger panel. 

 

S-100 expression can be nuclear and cytoplasmic.

S-100 is generally considered the most sensitive marker for melanoma (a few may argue vimentin), but has limitations in evaluation of lymph node tissue due to all of the background expression in dendritic cells.  MART-1 (Melan A) and HMB-45 are typically used more commonly in these situations.  As a general rule of thumb, the more epithelioid the melanoma, the more likely it will be to express MART-1 and HMB-45.  As melanomas become more “spindled” the less they tend to express HMB-45 and MART-1.  S-100 tends to retain expression in melanomas better as the pattern becomes more spindled compared to HMB-45 and MART-1

Wick, M. R. (2008). Immunohistochemical approaches to the diagnosis of undifferentiated malignant tumors. Annals of Diagnostic Pathology, 12(1), 72–84. doi:10.1016/j.anndiagpath.2007.10.003 

 

Kucher, C., Zhang, P. J., Acs, G., Roberts, S., & Xu, X. (2006). Can Melan-A replace S-100 and HMB-45 in the evaluation of sentinel lymph nodes from patients with malignant melanoma? Applied Immunohistochemistry & Molecular Morphology : AIMM / Official Publication of the Society for Applied Immunohistochemistry, 14(3), 324–327.