Comparison of Five Antibodies as Markers in Melanoma
Comparison of Five Antibodies as Markers in Melanoma
We determined the sensitivity and specificity of 3 novel antibodies (microphthalmia transcription factor [Mitf], Melan-A, and tyrosinase) as markers for melanoma in cytologic preparations and compared the results with those of commonly used markers (S-100 protein [S-100] and HMB-45). We stained 72 cell blocks from 40 patients with melanoma and 32 with nonmelanocytic malignant neoplasms with antibodies against S-100, HMB-45, Mitf, Melan-A, and tyrosinase. Histologic correlation was available in more than 95% of cases. Nuclear staining for Mitf and cytoplasmic staining for S-100, HMB-45, Melan-A, and tyrosinase in more than 10% of tumor cells was considered positive. All 3 novel markers demonstrated sensitivity superior to S-100 and HMB-45. HMB-45, Melan-A, and Mitf demonstrated specificities of 97%. S-100 protein and tyrosinase were less specific. Sensitivity and specificity for the combination Mitf+/Melan-A+ were 95% and 100%, respectively, whereas they were 80% and 100%, respectively, for S-100+/HMB-45+. Mitf, Melan-A, and tyrosinase are sensitive markers for epithelioid melanoma. Mitf and Melan-A seem more specific than S-100 and tyrosinase. An antibody panel consisting of Mitf and Melan-A is superior to a panel of S-100 and HMB-45 in the diagnosis of melanoma in cytologic specimens.
The cytologic diagnosis of metastatic melanoma can be challenging. Melanoma often manifests with a diverse cytologic appearance that may include a dyshesive single cell pattern or a cohesive cellular arrangement. The cell shape varies from epithelioid to spindled, or a mixture of epithelioid and spindle cell patterns might be seen. Furthermore, the cytologic features of melanoma often are shared with other poorly differentiated malignant neoplasms, including carcinomas, lymphomas, and sarcomas. In addition, metastatic melanoma can be found anywhere in the body and may manifest with a myriad of clinical signs and symptoms. Nevertheless, it is important to differentiate melanoma from nonmelanocytic malignant neoplasms because prognosis and therapy differ radically among these entities.
Immunocytochemical studies often are used as an aid in the diagnosis of melanoma. The most frequently used melanocytic markers in clinical practice are S-100 protein and HMB-45. Monoclonal antibody to S-100 protein, a calcium binding F-hand protein originally isolated from the brain, is a sensitive marker that reacts with more than 90% of melanomas. However, this protein also is present in adipocytes, chondrocytes, Schwann cells, and myoepithelial cells. Tumors derived from these tissues usually retain immunoreactivity to S-100 protein. Thus, S-100 protein reacts with a broad range of benign and malignant neoplasms, therefore limiting its specificity as a melanocytic marker. In addition, certain epithelial neoplasms such as mammary carcinoma may be positive for S-100 protein. Monoclonal antibody against HMB-45 antigen recognizes melanosome-specific gp100. Although it is quite specific for melanocytic neoplasms, HMB-45 is less sensitive than S-100 protein for identifying melanoma. Some melanomas, particularly the spindle cell and desmoplastic variants, fail to react with HMB-45. In addition, HMB-45 has been shown to react with other neural crest–derived tumors and occasionally with adenocarcinomas and other neoplasms.
Several new monoclonal antibodies raised against melanocytic differentiation antigens have become available for routine diagnostic use. These markers, which include microphthalmia transcription factor (Mitf; clone D5), tyrosinase (clone T311), and Melan-A (or MART-1; clone A103), are thought to be specific for melanocytic lesions. Mitf is a nuclear transcription factor critical for melanocyte development in the embryo and for survival of these melanocytes postnatally. Tyrosinase is a key enzyme involved in the early stages of melanin production and is present in cells of melanocytic lineage. Melan-A protein is a product of the MART-1 gene that is recognized by autologous cytotoxic T cells. It is a cytoplasmic protein that is expressed in mature melanocytes; however, its biologic function is unknown.
In a previous study, Dorvault et al demonstrated that Mitf was a sensitive and specific marker for melanomas in cytologic specimens and might be superior to the presently used melanocytic markers, S-100 protein and HMB-45. The purpose of the present study was to compare the diagnostic usefulness of the other novel melanoma markers, namely, tyrosinase and Melan-A with Mitf and with S-100 protein and HMB-45 as markers for melanoma in cytologic preparations.
We determined the sensitivity and specificity of 3 novel antibodies (microphthalmia transcription factor [Mitf], Melan-A, and tyrosinase) as markers for melanoma in cytologic preparations and compared the results with those of commonly used markers (S-100 protein [S-100] and HMB-45). We stained 72 cell blocks from 40 patients with melanoma and 32 with nonmelanocytic malignant neoplasms with antibodies against S-100, HMB-45, Mitf, Melan-A, and tyrosinase. Histologic correlation was available in more than 95% of cases. Nuclear staining for Mitf and cytoplasmic staining for S-100, HMB-45, Melan-A, and tyrosinase in more than 10% of tumor cells was considered positive. All 3 novel markers demonstrated sensitivity superior to S-100 and HMB-45. HMB-45, Melan-A, and Mitf demonstrated specificities of 97%. S-100 protein and tyrosinase were less specific. Sensitivity and specificity for the combination Mitf+/Melan-A+ were 95% and 100%, respectively, whereas they were 80% and 100%, respectively, for S-100+/HMB-45+. Mitf, Melan-A, and tyrosinase are sensitive markers for epithelioid melanoma. Mitf and Melan-A seem more specific than S-100 and tyrosinase. An antibody panel consisting of Mitf and Melan-A is superior to a panel of S-100 and HMB-45 in the diagnosis of melanoma in cytologic specimens.
The cytologic diagnosis of metastatic melanoma can be challenging. Melanoma often manifests with a diverse cytologic appearance that may include a dyshesive single cell pattern or a cohesive cellular arrangement. The cell shape varies from epithelioid to spindled, or a mixture of epithelioid and spindle cell patterns might be seen. Furthermore, the cytologic features of melanoma often are shared with other poorly differentiated malignant neoplasms, including carcinomas, lymphomas, and sarcomas. In addition, metastatic melanoma can be found anywhere in the body and may manifest with a myriad of clinical signs and symptoms. Nevertheless, it is important to differentiate melanoma from nonmelanocytic malignant neoplasms because prognosis and therapy differ radically among these entities.
Immunocytochemical studies often are used as an aid in the diagnosis of melanoma. The most frequently used melanocytic markers in clinical practice are S-100 protein and HMB-45. Monoclonal antibody to S-100 protein, a calcium binding F-hand protein originally isolated from the brain, is a sensitive marker that reacts with more than 90% of melanomas. However, this protein also is present in adipocytes, chondrocytes, Schwann cells, and myoepithelial cells. Tumors derived from these tissues usually retain immunoreactivity to S-100 protein. Thus, S-100 protein reacts with a broad range of benign and malignant neoplasms, therefore limiting its specificity as a melanocytic marker. In addition, certain epithelial neoplasms such as mammary carcinoma may be positive for S-100 protein. Monoclonal antibody against HMB-45 antigen recognizes melanosome-specific gp100. Although it is quite specific for melanocytic neoplasms, HMB-45 is less sensitive than S-100 protein for identifying melanoma. Some melanomas, particularly the spindle cell and desmoplastic variants, fail to react with HMB-45. In addition, HMB-45 has been shown to react with other neural crest–derived tumors and occasionally with adenocarcinomas and other neoplasms.
Several new monoclonal antibodies raised against melanocytic differentiation antigens have become available for routine diagnostic use. These markers, which include microphthalmia transcription factor (Mitf; clone D5), tyrosinase (clone T311), and Melan-A (or MART-1; clone A103), are thought to be specific for melanocytic lesions. Mitf is a nuclear transcription factor critical for melanocyte development in the embryo and for survival of these melanocytes postnatally. Tyrosinase is a key enzyme involved in the early stages of melanin production and is present in cells of melanocytic lineage. Melan-A protein is a product of the MART-1 gene that is recognized by autologous cytotoxic T cells. It is a cytoplasmic protein that is expressed in mature melanocytes; however, its biologic function is unknown.
In a previous study, Dorvault et al demonstrated that Mitf was a sensitive and specific marker for melanomas in cytologic specimens and might be superior to the presently used melanocytic markers, S-100 protein and HMB-45. The purpose of the present study was to compare the diagnostic usefulness of the other novel melanoma markers, namely, tyrosinase and Melan-A with Mitf and with S-100 protein and HMB-45 as markers for melanoma in cytologic preparations.
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