Melanosome specific antigen (MSA) is an incompletely characterized oligosaccharide side chain of a glycoconjugate, 10 kDa, detected by the monoclonal antibody HMB-45 (Human Melanoma, Black). The protein, also designated gp100, encoded by gene gp100-cl, is located in the premelanosomas in stage 1 and 2 and the non-melanised portion in stage 3. MSA is present in immature and activated melanocytes (due to, e.g., inflammation, increased vascularity or underlying tumour), but not in mature, resting melanocytes. There has been reports on HMB-45 reactivity in epithelial cells, this is probably due to contamination of the antibody.
Malignant melanoma are MSA positive in most cases (60-90%). However, spindle cell and desmoplastic malignant melanoma are MSA negative or only focally positive. MSA is found in varying proportions of benign melanocytic tumours like junction naevus and compound naevus. In these lesions, the epidermal part may be strongly stained while the dermal part is weakly staiend or unstained. Moreover MSA is detected in most caeses of blue naevus, cellular blue naevus, dysplastic naevus, Spitz naevus etc. MSA is also demonstrated in other tumours of melanocytic origin or differentiation (i.e., melanosome producing), such as clear cell sarcoma, proximal type epitheloid sarcoma, pulmonary blastoma, hepatoblastoma, phaeochromocytoma, melanotic neurofibroma and schwannoma and other neural crest derived tumours, as well as in so-called PEComas (perivascular epitheloid cell) derived from modified smooth muscle cells in the so-called tuberous sclerosis complex: angiomyolipoma, lymphangioleiomyoma(-tosis), and pulmonary sugar tumour, and cardiac rhabdomyoma. There are a few reports of aberrant MSA expression in adenocarcinoma. This is probably due to contamination of the antibody.
Being a highly specific marker, MSA has been widely used for the identification of melanocytic differentiation. However, MSA is generally a less sensitive marker than Melan-A and microphthalmia transcription factor (Mitf), particularly in the dermal component of benign melanocytic tumours and in spindle cell melanoma. MSA is useful for the identification of PEComa (together with alpha smooth muscle actin), but also here Melan-A may give a stronger staining.
It is difficult to identify any normal tissue expressing a consistent level of MSA to be used as a recommendable positive tissue control. Normal resting melanocytes in skin are typically not demonstrated by the mAb clone HMB-45. In order to validate a high sensitivity of the protocol an optimal calibration has to be performed. Tumours with both high and low level MSA expression must be used both during technical calibration of the protocol and as positive tissue controls. In the NordiQC assessments for MSA, blue nevus (run 7, 2003) and angiomyolipoma (run 40, 2014) thus have been superior to malignant melanomas. Using one of these neoplasias, the majority of neoplastic cells must show an at least weak to moderate and distinct granular cytoplasmic staining reaction. Kidney or appendix can be used as negative tissue controls; no staining reaction should be seen in the epithelial cells.
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