Table 2.
Immunohistochemical biomarkers with their function, current use, and staining pattern.
| Immunohistochemical Biomarker | Function | Current Use | Staining Pattern |
|---|---|---|---|
| S100 Protein Family | involved in multiple cellular processes such as cellular growth, cell cycle progression, cellular motility, calcium homeostasis, transcription, and protein phosphorylation [97,98] | highly sensitive (93%–100%) and stains most melanocytic lesions, but lacks specificity [97,127] | nuclear and cytoplasmic, strong and diffuse [97,128] |
| HMB 45 | monoclonal antibody against PMEL17 (gp100), plays role in organizational structure of melanoma [97] | very specific, lower sensitivity (70%–90%) than S100 [97] | cytoplasmic, finely granular [97] |
| Ki-67 | non-histone nuclear protein, proliferation marker [95] | useful in differentiating benign nevi from melanoma [95] | nuclear [95] |
| Melan A | assists in processing of PMEL17 for the formation of stage II melanosomes [97] | sensitivity is 85%–97% for primary melanoma, sensitivity is 57%–92% for metastatic melanoma, specificity is 95%–100% [97], not expressed in dendritic cells in lymph nodes [97] |
cytoplasmic [97] |
| CSPG4 | tissue development and cell motility [94,98] | more sensitive detection for metastatic melanoma than S100B, HMB 45, and MART-1 [94] | tumor cell membrane [129] |
| Tyrosinase | primary enzyme involved in melanin synthesis [97] | highly specific (97%–100%) [97,98] for primary melanoma [98], expressed in clear cell sarcomas, pigmented neurofibroma, and 20% of angiomyolipomas [97] |
cytoplasmic [97] |
| PNL2 | monoclonal antibody with unknown antigen, reacts with neutrophils and melanocytes [97] | positive in 75%–100% of primary metastatic and epithelioid melanomas, can stain positive in PEComas, clear cell sarcoma, and melanocytic schwannomas [97] | cytoplasmic [97] |
| MITF | neural crest cell differentiation [97] | limited use due to lack of specificity for melanoma but may be useful in an immunohistochemical panel [97] | nuclear [97,128,130] |
| SOX10 | embryonic determination of cell fate [97] | sensitive for primary and metastatic melanomas [97], positive in clear cell sarcomas and peripheral nerve sheath tumors [97] |
nuclear [97] |
| MC1R | G protein-coupled receptor family that controls pigment and plays role in skin phenotype and sensitivity [97] | sensitive for melanoma, not restricted to only melanocytes. Also present in neurons, hepatocyte, renal tubular cells, adrenal medullary cells, and myocardial cells [97,120] | cell surface and intracellular expression [120] |
| PRAME | part of the cancer testis antigen family, antigen recognition by T lymphocytes [123] | Stains positive in >75% of cells present in non-spindle cell cutaneous melanoma and is positive in 88%–94% of non-spindle cell cutaneous melanoma cases [124] | nuclear, diffuse reactivity [124] |
| pHH3 | correlates with mitosis looking for phosphorylation of histone H3 [95] | may overestimate mitoses due to melanocyte and non-melanocyte melanomas [95] | nuclear [131] |
| p16 | protein product of CDKN2A gene [95] | 50%–98% of melanomas show loss of nuclear staining [95] | nuclear, decreased in melanomas [95] |