Comparison of five antibodies as markers in the diagnosis of 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 stainingfor Mitf and cytoplasmic stainingfor 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 markersfor 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.

[1]  Tatum Ah,et al.  HMB-45-positive malignant lymphoma. A case report with literature review of aberrant HMB-45 reactivity. , 1991 .

[2]  Yao-Tseng Chen,et al.  T311--an anti-tyrosinase monoclonal antibody for the detection of melanocytic lesions in paraffin embedded tissues. , 2000, Pathology, research and practice.

[3]  M. Pinto.  An immunoperoxidase study of S-100 protein in neoplastic cells in serous effusions. Use as a marker for melanoma. , 1986, Acta cytologica.

[4]  S. Shin,et al.  Diagnostic utility of the monoclonal antibody A103 in fine-needle aspiration biopsies of the adrenal. , 2000, American journal of clinical pathology.

[5]  M. Gore,et al.  Fine needle aspiration biopsy of metastatic melanoma. A morphologic analysis of 174 cases. , 1986, Acta cytologica.

[6]  W. Johnston,et al.  Diagnosis of metastatic malignant melanoma by fine needle aspiration biopsy: a clinical and pathologic correlation of 298 cases. , 1986, Journal of the National Cancer Institute.

[7]  D. Ruiter,et al.  Immunohistochemistry in the evaluation of melanocytic tumors. , 1993, Seminars in diagnostic pathology.

[8]  E. Kaiserling,et al.  Ultrastructural localization of HMB‐45 binding sites , 1991, Journal of cutaneous pathology.

[9]  K. Ishak,et al.  Melanoma markers in angiomyolipoma of the liver and kidney: a comparative study. , 2009, Archives of pathology & laboratory medicine.

[10]  C. Farina,et al.  Cytotoxic T-lymphocyte clones from different patients display limited T-cell-receptor variable-region gene usage in HLA-A2-restricted recognition of the melanoma antigen Melan-A/MART-1. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[11]  L. J. Rubinstein,et al.  Recent applications of immunoperoxidase histochemistry in human neuro-oncology. An update. , 1987, Archives of pathology & laboratory medicine.

[12]  K. Busam,et al.  Melan-A, a new melanocytic differentiation marker. , 1999, Advances in anatomic pathology.

[13]  B. Scheithauer,et al.  Tumors of the peripheral nervous system , 1999 .

[14]  W. Gerald,et al.  A103: An anti-melan-a monoclonal antibody for the detection of malignant melanoma in paraffin-embedded tissues. , 1998, The American journal of surgical pathology.

[15]  Yao-Tseng Chen,et al.  Expression of melan-A (MART1) in benign melanocytic nevi and primary cutaneous malignant melanoma. , 1998, The American journal of surgical pathology.

[16]  Yao-Tseng Chen,et al.  Immunohistochemical and Reverse Transcription-Polymerase Chain Reaction Expression Analysis of Tyrosinase and Microphthalmia-Associated Transcription Factor in Angiomyolipomas , 2001, Applied immunohistochemistry & molecular morphology : AIMM.

[17]  A. Renshaw,et al.  A comparison of A103 and inhibin reactivity in adrenal cortical tumors: distinction from hepatocellular carcinoma and renal tumors. , 1998, Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc.

[18]  K. Franssila,et al.  Microphthalmia Transcription Factor in the Immunohistochemical Diagnosis of Metastatic Melanoma: Comparison With Four Other Melanoma Markers , 2001, The American journal of surgical pathology.

[19]  D. Fisher,et al.  Microphthalmia transcription factor , 2001, Cancer.

[20]  D. Fisher,et al.  Linking osteopetrosis and pycnodysostosis: Regulation of cathepsin K expression by the microphthalmia transcription factor family , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[21]  T. Isobe,et al.  [S 100 protein]. , 1984, Tanpakushitsu kakusan koso. Protein, nucleic acid, enzyme.

[22]  G. Herrera,et al.  S-100 protein expression by primary and metastatic adenocarcinomas. , 1988, American journal of clinical pathology.

[23]  X. Ji,et al.  Comparison of HMB-45 monoclonal antibody and S-100 protein in the immunohistochemical diagnosis of melanoma. , 1988, American journal of clinical pathology.

[24]  A. Folpe,et al.  Immunohistochemical Study of Microphthalmia Transcription Factor and Tyrosinase in Angiomyolipoma of the Kidney, Renal Cell Carcinoma, and Renal and Retroperitoneal Sarcomas: Comparative Evaluation With Traditional Diagnostic Markers , 2001, The American journal of surgical pathology.

[25]  S. Steinberg,et al.  Comparison of antibodies to MART‐1 and MelanA in fine‐needle aspiration samples of metastatic malignant melanoma , 2001, Diagnostic cytopathology.

[26]  A. Folpe,et al.  Microphthalmia Transcription Factor and Melanoma Cell Adhesion Molecule Expression Distinguish Desmoplastic/Spindle Cell Melanoma From Morphologic Mimics , 2001, The American journal of surgical pathology.

[27]  N. Sneige,et al.  Use of monoclonal antibody HMB-45 in the cytologic diagnosis of melanoma. , 1988, Acta cytologica.

[28]  T. Yoneda,et al.  Osteolytic bone metastasis in breast cancer , 2004, Breast Cancer Research and Treatment.

[29]  M. Dietel,et al.  Tyrosinase, melan-A, and KBA62 as markers for the immunohistochemical identification of metastatic amelanotic melanomas on paraffin sections. , 1998, Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc.

[30]  B. Kwon,et al.  Pigmentation genes: the tyrosinase gene family and the pmel 17 gene family. , 1993, The Journal of investigative dermatology.

[31]  J. Renauld,et al.  A new gene coding for a differentiation antigen recognized by autologous cytolytic T lymphocytes on HLA-A2 melanomas , 1994, The Journal of experimental medicine.

[32]  D. Ruiter,et al.  A monoclonal antibody specific for cells of the melanocyte lineage. , 1988, The American journal of pathology.

[33]  R. Lai,et al.  Cytodiagnosis of metastatic amelanotic melanomas by fine‐needle aspiration biopsy , 1998, Cancer.

[34]  G. Orchard.  Comparison of Immunohistochemical Labelling of Melanocyte differentiation Antibodies Melan-A, Tyrosinase and HMB 45 with NKIC3 and S100 Protein in the Evaluation of Benign Naevi and Malignant Melanoma , 2000, The Histochemical Journal.

[35]  Yao-Tseng Chen,et al.  Immunoreactivity for A103, an antibody to melan-A (Mart-1), in adrenocortical and other steroid tumors. , 1998, The American journal of surgical pathology.

[36]  K. Busam,et al.  Analysis of Microphthalmia Transcription Factor Expression in Normal Tissues and Tumors, and Comparison of Its Expression With S-100 Protein, gp100, and Tyrosinase in Desmoplastic Malignant Melanoma , 2001, The American journal of surgical pathology.

[37]  S. Fernando,et al.  Immunohistochemical Analysis Of Cutaneous Malignant Melanoma: Comparison of S‐100 protein, HMB‐45 monoclonal antibody and NKI/C3 monoclonal antibody , 1994, Pathology.

[38]  D. Brat,et al.  Microphthalmia transcription factor immunohistochemistry: a useful diagnostic marker in the diagnosis and detection of cutaneous melanoma, sentinel lymph node metastases, and extracutaneous melanocytic neoplasms. , 2001, Journal of the American Academy of Dermatology.

[39]  D. Fisher,et al.  Microphthalmia Transcription Factor: Not A Sensitive or Specific Marker for the Diagnosis of Desmoplastic Melanoma and Spindle Cell (Non-Desmoplastic) Melanoma , 2001, The American Journal of dermatopathology.

[40]  A. Gown,et al.  Anti-melanoma monoclonal antibody HMB45 identifies an oncofetal glycoconjugate associated with immature melanosomes. , 1992, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[41]  Yao-Tseng Chen,et al.  Serological analysis of Melan-A(MART-1), a melanocyte-specific protein homogeneously expressed in human melanomas. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[42]  Yao-Tseng Chen,et al.  Expression of melanocyte-associated markers gp-100 and Melan-A/MART-1 in angiomyolipomas , 1999, Virchows Archiv.

[43]  F. Marincola,et al.  Tyrosinase immunoreactivity in fine‐needle aspiration samples of metastatic malignant melanoma , 2000, Cancer.

[44]  M. Mihm,et al.  Microphthalmia transcription factor. A sensitive and specific melanocyte marker for MelanomaDiagnosis. , 1999, The American journal of pathology.

[45]  Pinto Mm.  An immunoperoxidase study of S-100 protein in neoplastic cells in serous effusions. Use as a marker for melanoma. , 1986 .

[46]  I. Ariel,et al.  Tumors of the peripheral nervous system , 1983, Seminars in surgical oncology.

[47]  Z. Orosz.  Melan‐A/Mart‐1 expression in various melanocytic lesions and in non‐melanocytic soft tissue tumours , 1999, Histopathology.

[48]  C. Goding,et al.  Melanocyte-specific expression of the human tyrosinase promoter: activation by the microphthalmia gene product and role of the initiator , 1994, Molecular and cellular biology.

[49]  M. Gonda,et al.  Production of recombinant MART-1 proteins and specific antiMART-1 polyclonal and monoclonal antibodies: use in the characterization of the human melanoma antigen MART-1. , 1997, Journal of immunological methods.

[50]  Alexander Marks,et al.  Role of antibody to S100 protein in diagnostic pathology. , 1983, American journal of clinical pathology.

[51]  M. Wick,et al.  Monoclonal Antibodies in Diagnostic Immunohistochemistry , 1989 .

[52]  P. Swanson,et al.  Recognition of malignant melanoma by monoclonal antibody HMB‐45. An immunohistochemical study of 200 paraffin‐embedded cutaneous tumors , 1988, Journal of cutaneous pathology.

[53]  J N Rodríguez-López,et al.  Tyrosinase: a comprehensive review of its mechanism. , 1995, Biochimica et biophysica acta.

[54]  S. Shibahara,et al.  Microphthalmia-associated transcription factor as a regulator for melanocyte-specific transcription of the human tyrosinase gene , 1994, Molecular and cellular biology.

[55]  P. Riley.  Molecules in focusMelanin , 1997 .

[56]  James A. Vaught,et al.  microphthalmia, a critical factor in melanocyte development, defines a discrete transcription factor family. , 1994, Genes & development.

[57]  Yao-Tseng Chen,et al.  Immunophenotyping of melanomas for tyrosinase: implications for vaccine development. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[58]  T. Nakajima,et al.  An immunoperoxidase study of S-100 protein distribution in normal and neoplastic tissues , 1982, The American journal of surgical pathology.