Melan-A is a melanocyte differentiation antigen, recognized by autologous cytotoxic T lymphocytes. Melan-A is also called MART-1 (melanoma antigen recognized by T cells). The Melan-A/MART-1 gene encodes this protein, 20-22 kDa, associated with endoplasmic reticulum and melanosomes. The function of the protein is unknown. Melan-A is expressed in all normal melanocytes and melanocyte cell lines. Using the monoclonal antibody A-103, staining is also seen in steroid hormone producing cells: adrenal cortex, granulosa and theca cells of the ovary and Leydig cells of the testis. This is due to cross reaction (as the Melan-A gene is not detected in these cells).
Melan A is expressed in 80-100% of malignant melanomas, including all primary cutaneous malignant melanomas and mucosal melanomas. In metastastic melanomas the staining may be patchy and somewhat less often positive than in the corresponding primary tumours. In desmoplastic melanoma the staining reaction is frequently patchy or negative. Cutaneous naevi (intradermal, compound, junctional) are Melan-A positive as are Spitz naevus, blue naevus etc. Melan-A is also demonstrated in other tumours of melanocytic origin or differentiation (i.e., melanosome producing), such as clear cell sarcoma, melanotic neurofibroma, melanotic schwannoma and other melanotic neural crest derived tumours, as well as in so-called PEComas (perivascular epitheloid cell tumour) derived from modified smooth muscle cells in the so-called tuberous sclerosis complex: angiomyolipoma, lymphangioleiomyoma(-tosis), and pulmonary sugar tumour. Using the antibody A-103, staining is furthermore seen in steroid hormone producing tumours: adrenocortical adenoma and carcinoma , sex cord-stromal tumour of the ovary and Leydig cell tumour of the testis.
Together with Microphtalmia transcription factor, Melan-A is one of the most valuable melanoma markers. In several studies, Melan-A has shown to be a more sensitive marker of melanocytic differentiation than e.g., Melanosoma Antigen and Tyrosinase, particularly regarding spindle cell and desmoplastic malignant melanomas. Melan-A is a more specific marker than S-100 protein. Melan-A should therefore be included in a standard melanoma panel. Melan-A is useful in confirming melanocytic differentiation of primary cutaneous tumours, differentiating these from neurothekeoma and benign fibrous histiocytoma. It is, however, of little help in differentiating melanocytic tumours with Schwannian differentiation from peripheral nerve sheath tumours. Melan-A is useful for the identification of PEComas (together with alpha smooth muscle actin). Using antibody A-103, Melan-A should also be included in panels for the diagnosis of e.g., clear cell tumours (for the identification of adrenal cortical tumours) and non-epithelial ovarian tumours.
Adrenal gland is a recommendable positive tissue control for MLA when using the mAb clone A103. A moderate to strong granular cytoplasmic staining reaction must be seen in virtually all epithelial cells throughout the adrenal cortex. However this reaction pattern can only be applied when a non-biotin based detection system is used, as the adrenal cortical cells are rich on endogenous biotin and a false positive staining reaction will thus mimic the specific reaction and eliminate the potential as a reliable positve control. In this assessment, four of the insufficient results showed a false negative staining reaction in the neoplasias, while positive staining reaction was seen in the adrenal cortical epithelial cells due to false positive staining of endogenous biotin by using a biotin-based detection system. Kidney is recommended as negative tissue control. No staining in the epithelial cells of tubules must be seen. Scattered epithelial cells may show a granular staining reaction caused by lipofuscin.
Selected references
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09.12.14 - HH/MV/LE