Melan-A

Synonyms: MART-1

by Assia Bassarova

Background

Melanoma associated self-antigen Melan-A/MART-1 (melanoma antigen A, and melanoma antigen recognized by T cells 1, respectively) is a melanocyte differentiation antigen, recognized by autologous cytotoxic T lymphocytes. The Melan-A/MART-1 gene encodes a 20-22 kDa type III signal-anchor protein that has been localized mainly to the endoplasmic reticulum and the transGolgi network. Melan-A/MART-1 is also detectable in the early stage I and II melanosomes of the melanoma cell lines. The function of the Melan-A/MART-1 polypeptide remains unknown.
Melan-A-specific CD8 T cells are frequently observed at the tumor site and tumor infiltrated lymph nodes, and can be readily identified in peripheral blood of both melanoma patients and healthy individuals. Melan-A-specific T cells have also been identified in peripheral blood of patients with vitiligo.

Staining in normal tissues:

Melan-A is expressed in all normal melanocytes and melanocyte cell lines. This property can be utilized to quantitate intraepidermal melanocytes in the evaluation of hypopigmentary disorders, such as vitiligo.
Most melanocytic junctional and compound nevi, with exception of neurotized nevi, are Melan-A positive throughout the whole thickness.
Using the monoclonal antibody A-103, variable immunoreactivity is observed in steroid hormone producing cells of adrenal cortex, granulosa and theca cells of the ovary and Leydig cells of the testis. The positive staining does not imply that Melan-A antigen is present in these cells, since Melan-A mRNA has not been found in them. The positive reaction is most likely due to cross reactivity with a similar epitope of a different gene.

Staining in tumors

Cutaneous naevi (intradermal, compound, junctional), Spitz nevi and blue nevi are Melan-A positive. Melan A is expressed in 80-100% of malignant melanomas, including all primary cutaneous malignant melanomas and mucosal melanomas. In desmoplastic melanoma the staining reaction is frequently patchy or negative. In metastastic melanomas the staining may be patchy and somewhat less often positive than in the corresponding primary tumours.
Like HMB-45, 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.
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.

Staining pattern

The melanocytes show strong granular cytoplasmic staining of cell body and the dendritic extensions. Strong, distinct granular cytoplasmic staining in virtually all cortical epithelial cells in the adrenal gland is observed with the A-103 antibody.

Control tissue

Normal skin and melanoma with low / heterogeneous Melan-A expression are recommended positive tissue controls. In normal skin, virtually all melanocytes should show strong positive reaction in the cytoplasm and weak to moderate reaction in the melanocytic dendrites in most melanocytes.

Application

  •  Together with S-100 / SOX-10 and Microphtalmia transcription factor, Melan-A is one of the most valuable melanocytic Melan-A is a more specific marker (in comparison to S-100 protein) and more sensitive marker of melanocytic differentiation especially regarding spindle cell and desmoplastic malignant melanomas. 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.
  • It is also an important marker in sentinel lymph node diagnostics and can be used as screening marker, detecting single cell or small intracapsular / subcapsular melanocytic aggregates.
  • 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.

Selected references

  1. Busam KJ, Jungbluth AA. Melan-A, a new melanocytic differentiation marker. Adv Anat Pathol. 1999 Jan; 6(1):12-8. doi: 10.1097/00125480-199901000-00002. PMID: 10197235.
  2. Romero P, Valmori D, Pittet MJ, et al. Antigenicity and immunogenicity of Melan-A/MART-1 derived peptides as targets for tumor reactive CTL in human melanoma. Immunol Rev. 2002 Oct;188:81-96. doi: 10.1034/j.1600-065x.2002.18808.x. PMID: 12445283.
  3. Pittet MJ, Zippelius A, Valmori D, et al. Melan-A/MART-1-specific CD8 T cells: from thymus to tumor. Trends Immunol. 2002 Jul;23(7):325-8. doi: 10.1016/s1471-4906(02)02244-5. PMID: 12103339.
  4. Shidham VB, Qi DY, Acker S, et al. Evaluation of micrometastases in sentinel lymph nodes of cutaneous melanoma: higher diagnostic accuracy with Melan-A and MART-1 compared with S-100 protein and HMB-45. Am J Surg Pathol. 2001 Aug;25(8):1039-46. doi: 10.1097/00000478-200108000-00008. PMID: 11474288.
  5. Prieto VG. Sentinel lymph nodes in cutaneous melanoma: handling, examination, and clinical repercussion. Arch Pathol Lab Med. 2010 Dec;134(12):1764-9. doi: 10.5858/2009-0502-RAR.1. PMID: 21128773.
  6. Venyo AK. A Review of the Literature on Extrarenal Retroperitoneal Angiomyolipoma. Int J Surg Oncol. 2016;2016:6347136. doi: 10.1155/2016/6347136. Epub 2016 Feb 17. PMID: 26989509; PMCID: PMC4773571.
  7. Busam KJ, Iversen K, Coplan KA, et al. Immunoreactivity for A103, an antibody to melan-A (Mart-1), in adrenocortical and other steroid tumors. Am J Surg Pathol. 1998 Jan;22(1):57-63. doi: 10.1097/00000478-199801000-00007. PMID: 9422316.
  8. Ordóñez NG. Value of melanocytic-associated immunohistochemical markers in the diagnosis of malignant melanoma: a review and update. Hum Pathol. 2014 Feb;45(2):191-205. doi: 10.1016/j.humpath.2013.02.007. Epub 2013 May 3. PMID: 23648379.