The Melan-A gene, also known as MART-1 (Melanoma Antigen Recognised by T-cells), was cloned from a melanoma cell line. Its subcellular location is not yet certain, but it is thought to be associated with melanosomes and endoplasmic reticulum. The gene is expressed in melanocytes of the skin and retina, malignant melanoma. The only cells, other than melanocytes, which express the gene are found in angiomyolipomas.
Two monoclonal antibodies have been raised; A103 and M2-7C10. Both are available commercially. Both are suitable for use on paraffin-embedded, formalin-fixed tissue. A103 has been the most extensively studied in histological material; MC-7C10 has been studied mainly in cytological preparations.
A103 shows immunoreactivity with:
Melanocytic cells
intraepidermal melanocytes
melanocytic naevi with the exception of neurotized naevi
primary cutaneous malignant melanomas
a minority of HMB-45-negative primary desmoplastic melanomas are positive with A-103
metastatic melanomas
in a series of 75 metastatic melanomas, 81% were positive with A-130
the rate of positivity is higher for epithelioid than for spindle cell tumours
Steroid hormone-producing tissues. This is not thought to be due to the expression of the Melan-A gene by these tissues (m-RNA for Melan-A is not detectable), but to cross-reactivity. There is some suggestion that immunoreactivity may deteriorate with time in stored blocks. M2-7C10 does not show positivity with these tissues.
the cortex of the adrenal gland
Leydig cells of the testis and Leydig cell tumours
Normal hilus cells and rete ovarii epithelium of the ovary
Leydig cells of the ovary
Granulosa cells of the ovary
staining is often weak and inconsistent
adrenocortical adenomas and carcinomas
staining is usually strong
Clear cell sugar tumours
confirming the melanocytic differentiation of primary cutaneous tumours and differentiating from neurothekeomas and benign fibrous histiocytomas. It is of little help in differentiating melanocytic tumours with Schwannian differentiation from peripheral nerve sheath tumours.
metastatic melanoma
sensitivity is probably greater than HMB-45.
adrenocortical tumours (A103 only; M2-7C10 does not stain these tissues.): 11/12cases3
differentiation from other carcinomas, particularly renal carcinomas and hepatocellular
to show true sex-cord differentiation in ovarian tumours
A103 is probably the most sensitive, followed by HMB-45, followed by M2-7C10
Clear cell sugar tumours
Advances in Anatomic Pathology 1999; 6:12-18
©SMUHT/PW Bishop