Melanoma

Immunohistochemistry

Typically positive for:

S-100. Positive in 95% of melanomas. Usually negative in signet-ring cell and rhabdoid melanomas. Usually positive in desmoplastic malignant melanomas.

NKIC3. Slightly more specific than S-100 but stains many non-melanocytic tumours.

HMB-45 Stains between 90% and 100% of primary melanomas, 80% or recurrent and metastatic melanomas and a lower proportion of spindle cell melanomas. Stains only minority of cases of desmoplastic malignant melanomas.

Melan-A. Rarely stains desmoplastic malignant melanomas.

Anti-tyrosinase. Sensitivity and specificity not yet adequately assessed, but appears to be less sensitive than S-100 and more sensitive than HMB-452. Stains only minority of cases of desmoplastic malignant melanomas.

PNL2: a initial report shows it is of similar sensitivity to other marker.s

MAGE expression by melanocytic cells appears to be restricted to malignant melanoma, with negativity in nevi6,7. MAGE-1 is less sensitive than are S-100, tyrosinase, Melan-A and HMB-4510: its has been claimed that expression shows an inverse relationship with expression of HMB-45 in non-desmoplastic melanomas and may therefore be useful in S-100 positive / HMB-45 negative tumours5; others have not reproduced this10. Its sensitivity in desmoplastic melanoma is lower. MAGE-3 has a low sensitivity of 25%6 to 40%7.

Vimentin: least useful; stains a wide variety of tumours

NSE: least useful; stains a wide variety of tumours.

CD117 tends to stain the in-situ component strongly, with loss of staining in deep dermal and nodular components4.

MDA-7 (melanoma differentiation associated gene 7) is a newly-described putative tumour suppressor gene sharing homology with IL-10. Its protein product can be detected by immunohistochemistry. It is highly expressed in normal melanocytes and benign nevi. Some initial studies show loss in thick melanomas. This has not been confirmed, but it is downregulated in metastatic melanoma. Its usefulness remains to be elucidated8.

WT1 has recently been proposed as a complementary marker for malignant melanoma.

Studies of conventional metastatic malignant melanomas gave the following comparison between melanoma markers:

	S-100	HMB-45	Tyrosinase	Melan A	Mitf	MAGE-1
negative	4% (12/266)1	14% (36/266)1	7% (19/266)1	12% (33/266)1	12% (31/266)1
<10% of tumour cells	2% (2/266)1	20% (52/266)1	3% (8/266)1	10% (26/266)1	3% (9/266)1
10% to 30% of tumour cells	4% (10/266)1	11% (30/266)1	7% (18/266)1	17% (445/266)1	15% (39/266)1
>30% of tumour cells	90% (240/266)1	55% (148/266)1	82% (221/226)1	61% (163/266)1	70% (187/266)1
strongly positive	52/5610	39/5610		42/5610		15/5610

Studies have been made of the value of the other markers in those melanomas which are negative for HMB-45

Melanoma markers have been compared in a series of vaginal, ovarian and sinonasal melanomas

Melan-A (clone A103) and MART-1 (clone M2-7C10) appear to be superior to either S-100 or HMB-45 for the diagnosis of micrometastases in sentienl lymph nodes3. However, a cocktail of HMB-45, Tyrosinase and Melan A / Mart-1 may optimise sensitivity, equal to that of S-100 but with superior specificity, particularly for the assessment of sentinel lymph nodes9.

Desmoplastic melanomas pose a particular diagnostic problem.

Aberrant immunophenotypes:

Cytokeratins. Most frequently positive with Cam5.2, in up to 10% of melanomas.

CEA. Usually seen with polyclonal antibodies.

EMA. Unusual in conventional melanomas, but has been reported in 43% of desmoplastic melanomas.

Desmin. Rarely positive.

SMA. Very rare in conventional melanomas and non-desmoplastic spindle cell melanomas, but is commonly seen in desmoplastic melanoma11.

NFP. Rarely positive.

GFAP. Has been seen in desmoplastic melanoma.

VS38.

CD68.

Factor XIIIa may be positive in desmoplastic melanoma11.

One study using TMAs compared primary melanomas with their respective metastases12.

	primary melanomas	metastatic from the same melanomas
Vimentin	66/7012	72/7312
bcl-2	43/7012	56/7312
CD117	51/7012	54/7312
CEA	30/7012	27/7312
EMA	14/7012	17/7312
S100	60/7012	58/7312
HMB45	51/7012	54/7312
AE1/AE3	7/7012	9/7312
Melan-A	34/7012	46/7312
TTF-1	1/7012	5/7312
CD99	19/7012	13/7312
Tyrosinase	21/7012	18/7312