Original contributionLoss of S100 antigenicity in metastatic melanoma
Introduction
Metastatic melanoma is one of the great mimickers in pathology. The diagnosis of metastatic melanoma is complicated by its ability to metastasize to any site and manifest variable histological patterns. In the absence of a known primary melanoma, accurate diagnosis requires a battery of immunostains. Although not specific, the S100 protein is expressed in all melanocytic cells and in 96% to 100% of malignant melanomas [1], [2], [3], [4]. Adjunct, but less sensitive, markers of melanoma include GP100 (86%), MART-1 (86%), tyrosinase (90%), and KBA-62 (87%) [3], [5], [6].
In up to 4% of metastatic melanomas, the S100 immunostain is negative [7], [8], [9]. One study that evaluated the immunoreactivity for S100 in 124 cases of metastatic melanoma showed a negative staining pattern in 2.4% of cases [6], whereas another study indicated a possible link between tumor metastasis and progression or atypical morphology with loss of immunoreactivity for S100 [8]. To develop criteria for accurately diagnosing S100-negative melanoma, we studied the evolution of S100 immunoreactivity in 1553 patients enrolled in ongoing clinical trials for metastatic melanoma in which multiple specimens were immunophenotyped during the course of their disease. We report on the primary site, histology, and immunophenotype of 17 cases that were negative for S100.
Section snippets
Selection of cases and immunohistochemistry
Melanoma cases in which S100 immunostaining was performed were identified with a keyword search performed on the National Cancer Institute (NCI) computerized database (1999-2004). Immunohistochemical studies were performed on formalin-fixed, paraffin-embedded tissue sections using heat-induced antigen retrieval. In brief, after deparaffinization, the slides were placed in a microwavable pressure cooker with 1.5 L of a 10 mmol/L concentration of citrate buffer (pH 6.0) containing 0.1% Tween 20
Results
A search of the NCI computerized database revealed that 2464 cases of melanoma representing 1553 patients were evaluated by immunohistochemical staining for S100 (Table 1). Of these, 19 metastatic lesions representing 17 unique patients were negative for S100. Of these 17 patients, 9 (53%) had a documented primary cutaneous melanoma. Four had a documented primary ocular melanoma (24%), whereas ocular melanoma represented only 6% of all patients reviewed. In the remaining 4 patients (24%) with
Discussion
The S100 family of proteins is a member of the calcium-binding EF-hand superfamily. Although the exact function of S100 proteins is not clear, they are involved in the regulation of a diverse host of cellular functions, including contraction, motility, growth, differentiation, cell cycle progression, transcription, and secretion [10], [11]. Certain S100 proteins are highly expressed in non–small cell lung cancer, breast cancer, gastric cancer, and lymphoma, whereas reduced levels of other
References (23)
- et al.
Standard immunostains for melanoma in sentinel lymph node specimens: which ones are most useful?
J Am Acad Dermatol
(2004) - et al.
HMB-45, S-100, NK1/C3, and MART-1 in metastatic melanoma
Hum Pathol
(2004) - et al.
The S100 protein family: history, function, and expression
Brain Res Bull
(1995) - et al.
S100 proteins in mouse and man: from evolution to function and pathology (including an update of the nomenclature)
Biochem Biophys Res Commun
(2004) - et al.
S100 proteins as cancer biomarkers with focus on S100B in malignant melanoma
Clin Biochem
(2004) - et al.
Inhibiting S100B restores p53 levels in primary malignant melanoma cancer cells
J Biol Chem
(2004) - et al.
Expression of gp100, MART-1, tyrosinase, and S100 in paraffin-embedded primary melanomas and locoregional, lymph node, and visceral metastases: implications for diagnosis and immunotherapy. A study conducted by the EORTC Melanoma Cooperative Group
J Pathol
(2001) - et al.
Tyrosinase, melan-A, and KBA62 as markers for the immunohistochemical identification of metastatic amelanotic melanomas on paraffin sections
Mod Pathol
(1998) - et al.
Immunohistochemical markers of melanocytic lesions: a review of their diagnostic usefulness
Am J Dermatopathol
(2002) - et al.
Immunohistochemical study of malanocytic differentiation antigens in cutaneous malignant melanoma. A comparison of six commercial antibodies and one non-commercial antibody in nodular melanoma, superficially spreading melanoma and lentigo maligna melanoma
Cesk Patol
(2004)
Morphological and immunophenotypic variations in malignant melanoma
Histopathology
Cited by (44)
Use of New Techniques in Addition to IHC Applied to the Diagnosis of Melanocytic Lesions, With Emphasis on CGH, FISH, and Mass Spectrometry
2017, Actas Dermo-SifiliograficasCitation Excerpt :The sensitivity of S100 in melanomas is very high in formalin-fixed tissues and thus, more than 90% of all primary melanomas, including desmoplastic variants, express S100 protein.24,25 However, its expression may be lost in metastases as well as in some spindle cell/desmoplastic melanomas.26,27 Also, since the specificity of S100 is not high, it is advisable to use it in conjunction with other melanocytic markers.
Melanoma cell galectin-1 ligands functionally correlate with malignant potential
2015, Journal of Investigative DermatologyCutaneous malignant melanoma with areas of de-differentiation simulating atypical fibroxanthoma: Antigen expression heterogeneity
2013, Diagnostic HistopathologyCitation Excerpt :S-100 immunostain is a very sensitive stain for melanoma and is reactive in 96–100% of melanoma. Loss of antigenicity has been reported in 1% of metastatic melanoma2 and rarely in primary melanomas.3 Both melanoma and sarcomatoid carcinoma can have connection to the overlying epidermis which can aid in recognizing them on H&E.
Cutaneous Melanoma: A Review of Multifactorial Pathogenesis, Immunohistochemistry, and Emerging Biomarkers for Early Detection and Management
2023, International Journal of Molecular Sciences