Tissue-Based Protein Biomarkers in Melanoma: Immunohistochemistry: (A) Diagnosis

  • Steven J. OhsieEmail author
  • Basil A. Horst
  • Alistair Cochran
  • Scott W. Binder
Part of the Current Clinical Pathology book series (CCPATH)


Melanocytic tumors are some of the most difficult neoplasms dealt with in the world of diagnostic pathology. While most melanocytic lesions are not diagnostically challenging, a significant minority show histopathological features that are ambiguous, making it difficult to assess their invasive and metastatic potential. Overdiagnosis of a benign nevus may cause significant morbidity; scarring following a wide excision in a cosmetically sensitive location such as the face, lymphedema secondary to lymph node dissection, and/or the adverse psychological impact of an erroneous malignant diagnosis. Underdiagnosis of a melanoma may provide the time during which a potentially curable malignancy advances to an untreatable illness. This chapter discusses the evaluation of protein markers by immunohistochemistry, as an aid in the diagnosis of melanoma.


Proliferate Cell Nuclear Antigen Malignant Peripheral Nerve Sheath Tumor Clear Cell Sarcoma Melanocytic Nevus Melanocytic Lesion 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Markovic SN, Erickson LA, Rao RD, et al. Malignant melanoma in the 21st century, part 1: epidemiology, risk factors, screening, prevention, and diagnosis. Mayo Clin Proc. 2007;82:364–80.PubMedGoogle Scholar
  2. 2.
    Elder DE. Lever’s histopathology of the skin. 10th ed. Philadelphia: Lippincott, Williams and Wilkins; 2009.Google Scholar
  3. 3.
    Banerjee SS, Harris M. Morphological and immunophenotypic variations in malignant melanoma. Histopathology. 2000;36:387–402.PubMedGoogle Scholar
  4. 4.
    Ohsie SJ, Sarantoupolous GP, Cochran AJ, Binder SW. Immunohistochemical characterstics of melanoma. J Cutan Pathol. 2008;35:433–44.PubMedGoogle Scholar
  5. 5.
    Cochran AJ, Wen DR. S-100 protein as a marker for melanocytic and other tumours. Pathology. 1985;17:340–5.PubMedGoogle Scholar
  6. 6.
    McKee PH, Calonje E, Granter SR. Pathology of the skin with clinical correlations. 3rd ed. Philadelphia: Elsevier Mosby; 2005.Google Scholar
  7. 7.
    Sujatha SEF, Johnson S, Bate J. Immunohistochemical analysis of cutaneous malignant melanoma: comparison of S-100 protein, HMB-45 monoclonal antibody and NKI/C3 monoclonal antibody. Pathology. 1994;26:16–9.Google Scholar
  8. 8.
    Bishop PW, Menasce LP, Yates AJ, Win NA, Banerjee SS. An immunophenotypic survey of malignant melanomas. Histopathology. 1993;23:159–66.PubMedGoogle Scholar
  9. 9.
    Dabbs DJ. Diagnostic immunohistochemistry. Philadelphia: Churchill Livingstone; 2002.Google Scholar
  10. 10.
    Kaufmann O, Koch S, Burghardt J, Audring H, Dietel M. Tyrosinase, Melan-A, and KBA62 as markers for the immunohistochemical identification of metastatic amelanotic melanomas on paraffin sections. Mod Pathol. 1998;11:740–6.PubMedGoogle Scholar
  11. 11.
    Ordonez NG, Xiaolong J, Hickey RC. Comparison of HMB-45 monoclonal antibody and S-100 protein in the immunohistochemical diagnosis of melanoma. Am J Clin Pathol. 1988;90:385–90.PubMedGoogle Scholar
  12. 12.
    Orchard GE. Comparison of immunohistochemical labeling of melanocyte differentiation antibodies melan-A, tyrosinase and HMB45 with NKIC3 and S100 protein in the evaluation of benign naevi and malignant melanoma. Histochem J. 2000;32:475–81.PubMedGoogle Scholar
  13. 13.
    Clarkson KS, Sturdgess IC, Molyneux AJ. The usefulness of tyrosinase in the immunohistochemical assessment of melanocytic lesions: a comparison of the novel T311 antibody (anti-tyrosinase) with S-100, HMB45, and A103 (anti-melan-A). J Clin Pathol. 2001;54:196–200.PubMedGoogle Scholar
  14. 14.
    Jungbluth AA, Busam KJ, Gerald WL, et al. A103: an anti-Melan-A monoclonal antibody for the detection of malignant melanoma in paraffin-embedded tissues. Am J Surg Pathol. 1998;22:595–602.PubMedGoogle Scholar
  15. 15.
    Sundram U, Harvell JD, Rouse RV, Natkunam Y. Expression of the B-cell proliferation marker MUM1 by melanocytic lesions and comparison with S100, gp100 (HMB45), and MelanA. Mod Pathol. 2003;16:802–10.PubMedGoogle Scholar
  16. 16.
    Fetsch PA, Marincola FM, Abati A. The new melanoma markers: MART-1 and Melan-A (the NIH experience). Am J Surg Pathol. 1999;23:607–9.PubMedGoogle Scholar
  17. 17.
    Miettinen M, Fernandez M, Franssila K, Gatalica Z, Lasota J, Sarlomo-Rikala M. Microphthalmia transcription factor in the immunohistochemical diagnosis of metastatic melanoma: comparison with four other melanoma markers. Am J Surg Pathol. 2001;25:205–11.PubMedGoogle Scholar
  18. 18.
    Busam KJ, Kucukgol D, Sato E, Frosina D, Teruya-Feldstein J, Jungbluth AA. Immunohistochemical analysis of novel monoclonal antibody PNL2 and comparison with other melanocyte differentiation markers. Am J Surg Pathol. 2005;29:400–6.PubMedGoogle Scholar
  19. 19.
    Jungbluth AA, Iversen K, Coplan K, et al. T311 – an anti-tyrosinase monoclonal antibody for the detection of melanocytic lesions in paraffin embedded tissues. Pathol Res Pract. 2000;196:235–42.PubMedGoogle Scholar
  20. 20.
    Boyle JL, Haupt HM, Stern JB, Multhaupt HAB. Tyrosinase expression in malignant melanoma, desmoplastic melanoma, and peripheral nerve tumors: an immunohistochemical study. Arch Pathol Lab Med. 2002;126:816–22.PubMedGoogle Scholar
  21. 21.
    King R, Googe PB, Weilbacher KN, Mihm Jr MC, Fisher DE. Microphthalmia transcription factor expression in cutaneous benign, malignant melanocytic, and nonmelanocytic tumors. Am J Surg Pathol. 2001;25:51–7.PubMedGoogle Scholar
  22. 22.
    Busam KJ, Iversen K, Coplan KC, Jungbluth AA. 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. Am J Surg Pathol. 2001;25:197–204.PubMedGoogle Scholar
  23. 23.
    Granter SR, Weilbaecher KN, Quigley C, Fisher DE. Role for microphthalmia transcription factor in the diagnosis of metastatic malignant melanoma. Appl Immunohistochem Mol Morphol. 2002;10:47–51.PubMedGoogle Scholar
  24. 24.
    Trefzer U, Rietz N, Chen Y, et al. SM5-1: a new monoclonal antibody which is highly sensitive and specific for melanocytic lesions. Arch Dermatol Res. 2000;292:583–9.PubMedGoogle Scholar
  25. 25.
    Wick MR, Swanson PE, Rocamora A. Recognition of malignant melanoma by monoclonal antibody HMB-45. An immunohistochemical study of 200 paraffin-embedded cutaneous tumors. J Cutan Pathol. 1988;15:201–7.PubMedGoogle Scholar
  26. 26.
    Argani P, Lae M, Hutchinson B, et al. Renal carcinomas with the t(6;11)(p21;q12): clinicopathologic features and demonstration of the specific alpha-TFEB gene fusion by immunohistochemistry, RT-PCR, and DNA PCR. Am J Surg Pathol. 2005;29:230–40.PubMedGoogle Scholar
  27. 27.
    Turhan T, Oner K, Yurtseven T, Akalin T, Ovul I. Spinal meningeal melanocytoma. Report of two cases and review of the literature. J Neurosurg. 2004;100(3 Suppl Spine):287–90.PubMedGoogle Scholar
  28. 28.
    O’Brien DF, Crooks D, Mallucci C, et al. Meningeal melanocytoma. Childs Nerv Syst. 2006;22:556–61.PubMedGoogle Scholar
  29. 29.
    Deavers MT, Malpica A, Ordonez NG, Silva EG. Ovarian steroid cell tumors: an immunohistochemical study including a comparison of calretinin with inhibin. Int J Gynecol Pathol. 2003;22:162–7.PubMedGoogle Scholar
  30. 30.
    Dim DC, Cooley LD, Miranda RN. Clear cell sarcoma of tendons and aponeuroses: a review. Arch Pathol Lab Med. 2007;131:152–6.PubMedGoogle Scholar
  31. 31.
    Swanson PE, Wick MR. Clear cell sarcoma: an immunohistochemical analysis of six cases and comparison with other epithelioid neoplasms of soft tissue. Arch Pathol Lab Med. 1989;113:55–60.PubMedGoogle Scholar
  32. 32.
    Mai KT, Belanger EC. Perivascular epithelioid cell tumour (PEComa) of the soft tissue. Pathology. 2006;38:415–20.PubMedGoogle Scholar
  33. 33.
    Hornick JL, Fletcher CDM. PEComa: what do we know so far? Histopathology. 2006;48:75–82.PubMedGoogle Scholar
  34. 34.
    Zubovits J, Buzney E, Yu L, Duncan LM. HMB-45, S-100, NK1/C3, and MART-1 in metastatic melanoma. Hum Pathol. 2004;35:217–23.PubMedGoogle Scholar
  35. 35.
    Chorny JA, Barr RJ. S100-positive spindle cells in scars: a diagnostic pitfall in the re-excision of desmoplastic melanoma. Am J Dermatopathol. 2002;24:309–12.PubMedGoogle Scholar
  36. 36.
    Busam K, Jungbluth A. The new melanoma markers: MART-1 and Melan-A (the NIH experience): author’s response. Am J Surg Pathol. 1999;23:610.Google Scholar
  37. 37.
    Hofbauer GFL, Kamarashev J, Geertsen R, Boni R, Dummer R. Tyrosinase immunoreactivity in formalin-fixed, paraffin-embedded primary and metastatic melanoma: frequency and distribution. J Cutan Pathol. 1998;25:204–9.PubMedGoogle Scholar
  38. 38.
    Makhlouf HR, Ishak KG, Shekar R, Sesterhenn IA, Young DY, Fanburg-Smith JC. Melanoma markers in angiomyolipoma of the liver and kidney. Arch Pathol Lab Med. 2002;126:49–55.PubMedGoogle Scholar
  39. 39.
    Roma AA, Magi-Galluzzi C, Zhou M. Differential expression of melanocytic markers in myoid, lipomatous, and vascular components of renal angiomyolipomas. Arch Pathol Lab Med. 2007;131:122–5.PubMedGoogle Scholar
  40. 40.
    King R, Weilbaecher KN, McGill G, Cooley E, Mihm M, Fisher DE. Microphthalmia transcription factor: a sensitive and specific melanocyte marker for melanoma diagnosis. Am J Pathol. 1999;155:731–8.PubMedGoogle Scholar
  41. 41.
    Prieto VG, Shea CR. Use of immunohistochemistry in melanocytic lesions. J Cutan Pathol. 2008;35(Suppl 10):1–10.PubMedGoogle Scholar
  42. 42.
    Chorny JA, Barr RJ, Kyshtoobayeva A, Jakowatz J, Reed RJ. Ki-67 and p53 expression in minimal deviation melanomas as compared with other nevomelanocytic lesions. Mod Pathol. 2003;16:525–9.PubMedGoogle Scholar
  43. 43.
    Rieger E, Hoffman-Wellenhof R, Soyer HP, et al. Comparison of proliferative activity as assessed by proliferating cell nuclear antigen (PCNA) and Ki-67 monoclonal antibodies in melanocytic skin lesions. J Cutan Pathol. 1993;20:229–36.PubMedGoogle Scholar
  44. 44.
    Vogt T, Zipperer KH, Vogt A, Holzel D, Landthaler M, Stolz W. P53-protein and Ki-67 antigen expression are both reliable biomarkers of prognosis in thick stage I nodular melanomas of the skin. Histopathology. 1997;30:57–63.PubMedGoogle Scholar
  45. 45.
    Korabiowska M, Brinck U, Middel P, et al. Proliferative activity in the progression of pigmented skin lesions, diagnostic and prognostic significance. Anticancer Res. 2000;20:1781–6.PubMedGoogle Scholar
  46. 46.
    Li LXL, Crotty KA, McCarthy SW, Palmer AA, Kril JJ. A zonal comparison of MIB1-Ki67 immunoreactivity in benign and malignant melanocytic lesions. Am J Dermatopathol. 2000;22:489–95.PubMedGoogle Scholar
  47. 47.
    Hazan C, Melzer K, Panageas KS, et al. Evaluation of the proliferation marker MIB-1 in the prognosis of cutaneous malignant melanoma. Cancer. 2002;95:634–40.PubMedGoogle Scholar
  48. 48.
    Henrique R, Azevedo R, Bento MJ, Domingues JC, Silva C, Jeronimo C. Prognostic value of Ki-67 expression in localized cutaneous malignant melanoma. J Am Acad Dermatol. 2000;43:991–1000.PubMedGoogle Scholar
  49. 49.
    Moretti S, Spallanzani A, Chiarugi A, Fabiani M, Pinzi C. Correlation of Ki-67 expression in cutaneous primary melanoma with prognosis in a prospective study: different correlation according to thickness. J Am Acad Dermatol. 2001;44:188–92.PubMedGoogle Scholar
  50. 50.
    Mihic-Probst D, Mnich CD, Oberholzer PA, et al. p16 status in primary malignant melanoma is associated with prognosis and lymph node status. Int J Cancer. 2006;118:2262–8.PubMedGoogle Scholar
  51. 51.
    Florenes VA, Maelandsmo GM, Faye R, Nesland JM, Holm R. Cyclin A expression in superficial spreading malignant melanomas correlates with clinical outcome. J Pathol. 2001;195:530–6.PubMedGoogle Scholar
  52. 52.
    Kanter-Lewensohn L, Hedblad MA, Wejde J, Larsson O. Immunohistochemical markers for distinguishing spitz nevi from malignant melanomas. Mod Pathol. 1997;10:917–20.PubMedGoogle Scholar
  53. 53.
    Tran TA, Ross JS, Carlson JA, Mihm Jr MC. Mitotic cyclins and cyclin dependent kinases in melanocytic lesions. Hum Pathol. 1998;29:1085–90.PubMedGoogle Scholar
  54. 54.
    Saenz-Santamaria MC, McNutt NS, Bogdany JK, Shea CR. P53 expression is rare in cutaneous melanomas. Am J Dermatopathol. 1995;17:344–9.PubMedGoogle Scholar
  55. 55.
    Stefanski C, Stefanski K, Antoniou C, et al. G1 cell cycle regulators in congenital melanocytic nevi. Comparison with acquired nevi and melanomas. J Cutan Pathol. 2008;35:799–808.Google Scholar
  56. 56.
    Woosley JT, Dietrich DR. Prognostic significance of PCNA grade in malignant melanoma. J Cutan Pathol. 1993;20:498–503.PubMedGoogle Scholar
  57. 57.
    Kanoko M, Ueda M, Ichihashi M. PCNA expression and nucleolar organizer regions in malignant melanoma and nevus cell nevus. Kobe J Med Sci. 1994;40:107–23.PubMedGoogle Scholar
  58. 58.
    Niemann TH, Argenyi ZB. Immunohistochemical study of spitz nevi and malignant melanoma with use of antibody to proliferating cell nuclear antigen. Am J Dermatopathol. 1993;15:441–5.PubMedGoogle Scholar
  59. 59.
    Florell SR, Bowen AR, Hanks AN, et al. Proliferation, apoptosis, and surviving expression in a spectrum of melanocytic nevi. J Cutan Pathol. 2005;32:45–9.PubMedGoogle Scholar
  60. 60.
    Niezabitowski A, Czajecki K, Rys J, et al. Prognostic evaluation of cutaneous malignant melanoma: a clinicopathologic and immunohistochemical study. J Surg Oncol. 1999;70:150–60.PubMedGoogle Scholar
  61. 61.
    Reddy VB, Gattuso P, Aranha G, Carson HJ. Cell proliferation markers in predicting metastases in malignant melanoma. J Cutan Pathol. 1995;22:248–51.PubMedGoogle Scholar
  62. 62.
    Karjalainen JM, Eskelinen MJ, Kellokoski JK, Reinikainen M, Alhava EM, Kosma VM. P21WAF1/CIP1 expression in stage I cutaneous malignant melanoma: its relationship with p53, cell proliferation and survival. Br J Cancer. 1999;79:895–902.PubMedGoogle Scholar
  63. 63.
    Bales ES, Dietrich C, Bandyopadhyay D, et al. High levels of expression of p27KIP1 and cyclin E in invasive primary malignant melanomas. J Invest Dermatol. 1999;113:1039–46.PubMedGoogle Scholar
  64. 64.
    Georgieva J, Sinha P, Schadendorf D. Expression of cyclins and cyclin dependent kinases in human benign and malignant melanocytic lesions. J Clin Pathol. 2001;54:229–35.PubMedGoogle Scholar
  65. 65.
    Florenes VA, Faye RS, Maelandsmo GM, Nesland JM, Holm R. Levels of cyclin D1 and D3 in malignant melanoma: deregulated cyclin D3 expression is associated with poor clinical outcome in superficial melanoma. Clin Cancer Res. 2000;6:3614–20.PubMedGoogle Scholar
  66. 66.
    Karim RZ, Li W, Sanki A, et al. Reduced p16 and increased cyclin D1 and pRb expression are correlated with progression in cutaneous melanocytic tumors. Int J Surg Pathol. 2009;17:361–7.PubMedGoogle Scholar
  67. 67.
    Demirkin NC, Kesen Z, Akdag B, Larue L, Delmas V. The effect of the sun on expression of β–catenin, p16, and cyclin D1 proteins in melanocytic lesions. Clin Exp Dermatol. 2007;32:733–9.Google Scholar
  68. 68.
    Ramirez JA, Guitart J, Rao MS, Diaz LK. Cyclin D1 expression in melanocytic lesions of the skin. Ann Diagn Pathol. 2005;9:185–8.PubMedGoogle Scholar
  69. 69.
    Straume O, Sviland L, Akslen LA. Loss of nuclear p16 protein expression correlates with increased tumor cell proliferation (Ki-67) and poor prognosis in patients with vertical growth phase melanoma. Clin Cancer Res. 2000;6:1845–53.PubMedGoogle Scholar
  70. 70.
    Bachmann IM, Straume O, Akslen LA. Altered expression of cell cycle regulators cyclin D1, p14, p16, CDK4 and Rb in nodular melanomas. Int J Oncol. 2004;25:1559–65.PubMedGoogle Scholar
  71. 71.
    Talve L, Sauroja I, Collan Y, Punnonen K, Ekfors T. Loss of expression of the p16INK4/CDKN2 gene in cutaneous malignant melanoma correlates with tumor cell proliferation and invasive stage. Int J Cancer. 1997;74:255–9.PubMedGoogle Scholar
  72. 72.
    Pavey SJ, Cummings MC, Whiteman DC, et al. Loss of p16 expression is associated with histological features of melanoma invasion. Melanoma Res. 2002;12:539–47.PubMedGoogle Scholar
  73. 73.
    Mihic-Probst D, Saremaslani P, Komminoth P, Heitz PU. Immunostaining for the tumour suppressor gene p16 product is a useful marker to differentiate melanoma metastasis from lymph-node nevus. Virchows Arch. 2003;443:745–51.PubMedGoogle Scholar
  74. 74.
    Funk JO, Schiller PI, Barrett MT, Wong DJ, Kind P, Sander CA. P16INK4a expression is frequently decreased and associated with 9p21 loss of heterozygosity in sporadic melanoma. J Cutan Pathol. 1998;25:291–6.PubMedGoogle Scholar
  75. 75.
    Wang YL, Uhara H, Yamazaki Y, Nikaido T, Saida T. Immunohistochemical detection of CDK4 and p16INK4 proteins in cutaneous malignant melanoma. Br J Dermatol. 1996;134:269–75.PubMedGoogle Scholar
  76. 76.
    Sparrow LE, Eldon MJ, English DR, Heenan PJ. P16 and p21WAF1 protein expression in melanocytic tumors by immunohistochemistry. Am J Dermatopathol. 1998;20:255–61.PubMedGoogle Scholar
  77. 77.
    Alonso SR, Ortiz P, Pollan M, et al. Progression in cutaneous malignant melanoma is associated with distinct expression profiles. Am J Pathol. 2004;164:193–203.PubMedGoogle Scholar
  78. 78.
    Florenes VA, Maelandsmo GM, Kerbel RS, Slingerland JM, Nesland JM, Holm R. Protein expression of the cell-cycle inhibitor p27Kip1 in malignant melanoma: inverse correlation with disease-free survival. Am J Pathol. 1998;153:305–12.PubMedGoogle Scholar
  79. 79.
    Ivan D, Diwan AH, Esteva FJ, Prieto VG. Expression of cell cycle inhibitor p27Kip1 and its inactivator Jab1 in melanocytic lesions. Mod Pathol. 2004;17:811–8.PubMedGoogle Scholar
  80. 80.
    Morgan MB, Cowper SE. Expression of p-27 (kip1) in nevi and melanomas. Am J Dermatopathol. 1999;21:121–4.PubMedGoogle Scholar
  81. 81.
    Li Q, Murphy M, Ross J, Sheehan C, Carlson JA. Skp2 and p27kip1 expression in melanocytic nevi and melanoma: an inverse relationship. J Cutan Pathol. 2004;31:633–42.PubMedGoogle Scholar
  82. 82.
    Curry JL, Richards HW, Huttenbach YT, Medrano EE, Reed JA. Different expression patterns of p27KIP1 and p57KIP2 in benign and malignant neoplasms and in cultured human melanocytes. J Cutan Pathol. 2009;36:197–205.PubMedGoogle Scholar
  83. 83.
    Talve K, Kainu J, Collan Y, Ekfors T. Immunohistochemical expression of p53 protein, mitotic index and nuclear morphometry in primary malignant melanoma of the skin. Pathol Res Pract. 1996;192:825–33.PubMedGoogle Scholar
  84. 84.
    Korabiowska M, Betke H, Kellner S, Stachura J, Schauer A. Differential expression of growth arrest, DNA damage genes and tumour suppressor gene p53 in naevi and malignant melanomas. Anticancer Res. 1997;17:3697–700.PubMedGoogle Scholar
  85. 85.
    Korabiowska M, Brinck U, Hoenig JF, et al. Significance of p-53 antigen in malignant melanomas and naevi of the head and neck area. Anticancer Res. 1995;15:885–90.PubMedGoogle Scholar
  86. 86.
    Trotter MJ, Tang L, Tron VA. Overexpression of the cyclin-dependent kinase inhibitor p21WAF1/CIP1 in human cutaneous malignant melanoma. J Cutan Pathol. 1997;24:265–71.PubMedGoogle Scholar
  87. 87.
    Zhuang L, Lee CS, Scolyer RA, et al. Mcl-1, Bcl-XL and Stat3 expression are associated with progression of melanoma whereas Bcl-2, AP-2 and MITF levels decrease during progression of melanoma. Mod Pathol. 2007;20:416–26.PubMedGoogle Scholar
  88. 88.
    Dai DL, Martinka M, Li G. Prognostic significance of activated Akt expression in melanoma: a clinicopathologic study of 292 cases. J Clin Oncol. 2005;23:1473–82.PubMedGoogle Scholar
  89. 89.
    Dhawan P, Singh AB, Ellis DL, Richmond A. Constitutive activation of Akt/protein kinase B in melanoma leads to up-regulation of nuclear factor-κB and tumor progression. Cancer Res. 2002;62:7335–42.PubMedGoogle Scholar
  90. 90.
    Kantrow SM, Boyd AS, Ellis DL, et al. Expression of activated Akt in benign nevi, Spitz nevi and melanomas. J Cutan Pathol. 2007;34:593–6.PubMedGoogle Scholar
  91. 91.
    Bachmann IM, Puntervoll HE, Otte AP, Akslen LA. Los of BMI-1 expression is associated with clinical progress of malignant melanoma. Mod Pathol. 2008;21:583–90.PubMedGoogle Scholar
  92. 92.
    Jungbluth AA, Chen YT, Stockert E, et al. Immunohistochemical analysis of NY-ESO-1 antigen expression in normal and malignant human tissues. Int J Cancer. 2001;92:856–60.PubMedGoogle Scholar
  93. 93.
    Prasad ML, Jungbluth AA, Patel SG, Iversen K, Hoshaw-Woodard S, Busam KJ. Expression and significance of cancer testis antigens in primary mucosal melanoma of the head and neck. Head Neck. 2004;26:1053–7.PubMedGoogle Scholar
  94. 94.
    Luftl M, Schuler G, Jungbluth AA. Melanoma or not? Cancer testis antigens may help. Br J Dermatol. 2004;151:1213–8.PubMedGoogle Scholar
  95. 95.
    van den Oord JJ. Expression of CD26/dipeptidyl-peptidase IV in benign and malignant pigment-cell lesions of the skin. Br J Dermatol. 1998;138:615–21.PubMedGoogle Scholar
  96. 96.
    Sviatoha V, Rundgren A, Tani E, Hansson J, Kleina R, Skoog L. Expression of CD40, CD44, bcl-2 antigens and rate of cell proliferation on fine needle aspirates from metastatic melanoma. Cytopathology. 2002;13:11–21.PubMedGoogle Scholar
  97. 97.
    van den Oord JJ, Maes A, Stas M, et al. CD40 is a prognostic marker in primary cutaneous malignant melanoma. Am J Pathol. 1996;149:1953–61.PubMedGoogle Scholar
  98. 98.
    Kuźbicki Ł, Aładowicz E, Chwirot B. Cyclin-dependent kinase 2 expression in human melanomas and benign melanocytic skin lesions. Melanoma Res. 2006;16:435–44.PubMedGoogle Scholar
  99. 99.
    Ilmonen S, Vaheri A, Asko-Seljavaara S, Carpen O. Ezrin in primary cutaneous melanoma. Mod Pathol. 2005;18:503–10.PubMedGoogle Scholar
  100. 100.
    Anastassiou G, Coupland SE, Stang A, Boeloeni R, Schilling H, Bornfeld N. Expression of Fas and Fas ligand in uveal melanoma: biological implication and prognostic value. J Pathol. 2001;194:466–72.PubMedGoogle Scholar
  101. 101.
    Redondo P, Solano T, Vazquez B, Bauza A, Idoate M. Fas and Fas ligand: expression and soluble circulating levels in cutaneous malignant melanoma. Br J Dermatol. 2002;147:80–6.PubMedGoogle Scholar
  102. 102.
    Bullani RR, Wehrli P, Viard-Leveugle I, et al. Frequent downregulation of Fas (CD95) expression and function in melanoma. Melanoma Res. 2002;12:263–70.PubMedGoogle Scholar
  103. 103.
    Bozdogan N, Bozdogan O, Pak I, Atasoy P. FAS, FAS ligand, tumor infiltrating lymphocytes, and macrophages in malignant melanoma: an immunohistochemical study. Int J Dermatol. 2010;49:761–7.PubMedGoogle Scholar
  104. 104.
    Bullani RR, Huard B, Viard-Leveugle I, et al. Selective expression of FLIP in malignant melanocytic skin lesions. J Invest Dermatol. 2001;117:360–4.PubMedGoogle Scholar
  105. 105.
    Gelsleichter L, Gown AM, Zarbo RJ, Wang E, Coltrera MD. P53 and mdm-2 expression in malignant melanoma: an immunohistochemical study of expression of p53, mdm-2, and markers of cell proliferation in primary versus metastatic tumors. Mod Pathol. 1995;8:530–5.PubMedGoogle Scholar
  106. 106.
    Polsky D, Bastian BC, Hazan C, et al. HDM2 protein overexpression, but not gene amplification, is related to tumorigenesis of cutaneous melanoma. Cancer Res. 2001;61:7642–6.PubMedGoogle Scholar
  107. 107.
    Polsky D, Melzer K, Hazan C, et al. HDM2 protein overexpression and prognosis in primary malignant melanoma. J Natl Cancer Inst. 2002;94:1803–6.PubMedGoogle Scholar
  108. 108.
    Kageshita T, Hirai S, Ono T, Hicklin DJ, Ferrone S. Down-regulation of HLA class I antigen-processing molecules in malignant melanoma: association with disease progression. Am J Pathol. 1999;154:745–54.PubMedGoogle Scholar
  109. 109.
    Kageshita T, Kawakami Y, Ono T. Clinical significance of MART-1 and HLA-A2 expression and CD8+ T cell infiltration in melanocytic lesions in HLA-A2 phenotype patients. J Dermatol Sci. 2001;25:36–44.PubMedGoogle Scholar
  110. 110.
    Ruiter DJ, Bergman W, Welvaart K, et al. Immunohistochemical analysis of malignant melanomas and nevocellular nevi with monoclonal antibodies to distinct monomorphic determinants of HLA antigens. Cancer Res. 1984;44:3930–5.PubMedGoogle Scholar
  111. 111.
    Denicourt C, Saenz CC, Datnow B, Cui XS, Dowdy SF. Relocalized p27Kip1 tumor suppressor functions as a cytoplasmic metastatic oncogene in melanoma. Cancer Res. 2007;67:9238–43.PubMedGoogle Scholar
  112. 112.
    Hilliard NJ, Krahl D, Sellhayer K. p16 expression differentiates between desmoplastic Spitz nevus and desmoplastic melanoma. J Cutan Pathol. 2009;36:753–9.PubMedGoogle Scholar
  113. 113.
    Maelandsmo GM, Holm R, Fodstad O, Kerbel RS, Florenes VA. Cyclin kinase inhibitor p21WAF1/CIP1 in malignant melanoma: reduced expression in metastatic lesions. Am J Pathol. 1996;149:1813–22.PubMedGoogle Scholar
  114. 114.
    Sanki A, Li W, Colman M, et al. Reduced expression of p16 and p27 is correlated with tumor progression in cutaneous melanoma. Pathology. 2007;39:551–7.PubMedGoogle Scholar
  115. 115.
    Woenckhaus C, Maile S, Uffmann S, et al. Expression of Skp2 and p27KIP1 in naevi and malignant melanoma of the skin and its relation to clinical outcome. Histol Histopathol. 2005;20:501–8.PubMedGoogle Scholar
  116. 116.
    Sparrow LE, English DR, Taran JM, Heenan PJ. Prognostic significance of MIB-1 proliferative activity in thin melanomas and immunohistochemical analysis of MIB-1 proliferative activity in melanocytic tumors. Am J Dermatopathol. 1998;20:12–6.PubMedGoogle Scholar
  117. 117.
    Cantley LC. The phosphoinositide 3-kinase pathway. Science. 2002;296:1655–7.PubMedGoogle Scholar
  118. 118.
    Slipicevic A, Holm R, Nguyen MT, et al. Expression of activated Akt and PTEN in malignant melanomas: relationship with clinical outcome. Am J Clin Pathol. 2005;124:528–36.PubMedGoogle Scholar
  119. 119.
    Flørenes VA, Mælandsmo GM, Holm R. Expression of activated TrkA protein in melanocytic tumors: relationship to cell proliferation and clinical outcome. Am J Clin Pathol. 2004;122:412–20.PubMedGoogle Scholar
  120. 120.
    Stefanski C, Stefanski K, Antoniou C, et al. Cell cycle and apoptosis regulators in Spitz nevi: comparison with melanomas and common nevi. J Am Acad Dermatol. 2007;56:815–24.Google Scholar
  121. 121.
    Garrido-Ruiz MC, Requena L, Ortiz P, et al. The immunohistochemical profile of Spitz nevi and conventional (non-Spitzoid) melanomas: a baseline study. Mod Pathol. 2010;23:1–10.Google Scholar
  122. 122.
    Vollmer RT. Use of bayes rule and MIB-1 proliferation index to discriminate Spitz nevus from malignant melanoma. Am J Clin Pathol. 2004;122:499–505.PubMedGoogle Scholar
  123. 123.
    Kapur P, Selim MA, Roy LC, et al. Spitz nevi and atypical Spitz nevi/tumors: a histologic and immunohistochemical analysis. Mod Pathol. 2005;18:197–204.PubMedGoogle Scholar
  124. 124.
    Herron MD, Vanderhooft SL, Smock K, et al. Proliferative nodules in congenital melanocytic nevi: a clinicopathologic and immunohistochemical analysis. Am J Surg Pathol. 2004;28:1017–25.PubMedGoogle Scholar
  125. 125.
    Kucher C, Zhang PJ, Pasha T, et al. Expression of Melan-A and Ki-67 in desmoplastic melanoma and desmoplastic nevi. Am J Dermatopathol. 2004;26:452–7.PubMedGoogle Scholar
  126. 126.
    Radfar A, Stefanato CM, Ghosn S, Bhawan J. NGFR-positive desmoplastic melanomas with focal or absent S-100 staining: further evidence supporting the use of both NGFR and S-100 as a primary immunohistochemical panel for the diagnosis of desmoplastic melanomas. Am J Dermatopathol. 2006;28:162–7.PubMedGoogle Scholar
  127. 127.
    Kanik AB, Yaar M, Bhawan J. p75 nerve growth factor receptor staining helps identify desmoplastic and neurotropic melanoma. J Cutan Pathol. 1996;23:205–10.PubMedGoogle Scholar
  128. 128.
    Satori I, Burrows R, Agoff SN, Piepkorn M, Bothwell M, Schmidt R. The p75 neurotrophin receptor, relative to other schwann cell and melanoma markers, is abundantly expressed in spindled melanomas. Am J Dermatopathol. 2001;23:288–94.Google Scholar
  129. 129.
    Nonaka D, Chiriboga L, Rubin BP. Sox10: a pan-schwannian and melanocytic marker. Am J Surg Pathol. 2008;32:1291–8.PubMedGoogle Scholar
  130. 130.
    Ramos-Herberth FI, Karamchandani J, Kim J, Dadras SS. SOX10 immunostaining distinguishes desmoplastic melanoma from excision scar. J Cutan Pathol. 2010;37:944–52.PubMedGoogle Scholar
  131. 131.
    Fanburg-Smith JC, Miettinen M. Low affinity nerve growth factor receptor (p75) in dermatofibrosarcoma protuberans and other nonneural tumors: a study of 1,150 tumors and fetal and adult normal tissues. Hum Pathol. 2001;32:976–83.PubMedGoogle Scholar
  132. 132.
    Carlson JA, Ross JS, Slominski AJ. New techniques in dermatopathology that help to diagnose and prognosticate melanoma. Clin Dermatol. 2009;27:75–102.PubMedGoogle Scholar
  133. 133.
    Kashani-Sabet M, Rangela J, Torabian S, et al. A multi-marker assay to distinguish malignant melanomas from benign nevi. Proc Natl Acad Sci USA. 2009;106:6268–72.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Steven J. Ohsie
    • 1
    Email author
  • Basil A. Horst
    • 2
  • Alistair Cochran
    • 3
  • Scott W. Binder
    • 4
  1. 1.Affiliated Pathologists Medical Group/Pathology, Inc.TorrenceUSA
  2. 2.Departments of Dermatology, Pathology and Cell BiologyColumbia University Medical CenterNew YorkUSA
  3. 3.Departments of Pathology and Laboratory Medicine and SurgeryDavid Geffen School of Medicine at the University of CaliforniaLos AngelesUSA
  4. 4.Department of Pathology and Laboratory MedicineDavid Geffen School of Medicine at the University of CaliforniaLos AngelesUSA

Personalised recommendations