Diagnostic and prognostic biomarkers in melanoma

Journal of Clinical and Aesthetic Dermatology

Volumn 7, Issue 6, 2014, Pages 13-24

  Weinstein, David ^a   Leininger, Jennifer ^a   Hamby, Carl ^a   Safai, Bijan ^a  

^a NEW YORK MEDICAL COLLEGE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ADENYLATE CYCLASE; BIOLOGICAL MARKER; C REACTIVE PROTEIN; CD146 ANTIGEN; CELL ADHESION MOLECULE; DNA; INTERLEUKIN 6; KI 67 ANTIGEN; LACTATE DEHYDROGENASE; MELAN A; MELANOMA ANTIGEN; METALLOTHIONEIN; MICROPHTHALMIA ASSOCIATED TRANSCRIPTION FACTOR; MONOPHENOL MONOOXYGENASE; PENTRAXIN; PROTEIN S 100; PROTEOCHONDROITIN SULFATE; PROTEOCHONDROITIN SULFATE 4; TRANSCRIPTION FACTOR 3; UNCLASSIFIED DRUG; VASCULOTROPIN;

CANCER DIAGNOSIS; CANCER GROWTH; CANCER PROGNOSIS; CANCER SURVIVAL; CELL ADHESION; CELL DIFFERENTIATION; CELL GROWTH; CELL SURVIVAL; DIAGNOSTIC TEST ACCURACY STUDY; ENDOPLASMIC RETICULUM; FLUORESCENCE IN SITU HYBRIDIZATION; GLIA CELL; HISTIOCYTE; HUMAN; LANGERHANS CELL; LYMPHOCYTE; MELANOCYTE; MELANOCYTIC NEVUS; MELANOMA; MELANOSOME; PERIPHERAL LYMPHOCYTE; REVIEW; SCHWANN CELL; SENSITIVITY AND SPECIFICITY; TRANS GOLGI NETWORK;

EID: 84903393920     PISSN: 19412789     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (194)

1. The Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute. SEER Stat Fact Sheets: Melanoma of the Skin. http://www.seer.cancer.gov/statfacts/html/melan.html. Accessed on May 26, 2014.
2. Howlader N, Noone AM, Krapcho M, et al (eds). SEER Cancer Statistics Review, 1975-2011, National Cancer Institute. Bethesda, MD. http://seer.cancer. gov/csr/1975-2011/, based on November 2013 SEER data submission, posted to the SEER website April 2014.
3. Robert C, Thomas L, Bondarenko I, et al. Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N Engl J Med. 2011;364(26):2517-2526.
4. Chapman PB, Hauschild A, Robert C, et al. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med. 2011;364(26):2507-2516.
5. Banerjee SS, Harris M. Morphological and immunophenotypic variations in malignant melanoma. Histopathology. 2000;36(5):387-402. (Pubitemid 30311621)
6. Anstey A, Cerio R, Ramnarain N, et al. Desmoplastic malignant melanoma. An immunocytochemical study of 25 cases. Am J Dermatopathol. 1994;16(1):14-22. (Pubitemid 24062747)
7. Dorvault CC, Weilbaecher KN, Yee H, et al. Microphthalmia transcription factor: a sensitive and specific marker for malignant melanoma in cytologic specimens. Cancer. 2001;93(5):337-343. (Pubitemid 32995218)
8. Fernando SS, 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(1):16-19. (Pubitemid 24047196)
9. Hofbauer GF, Kamarashev J, Geertsen R, et al. Tyrosinase immunoreactivity in formalin-fixed, paraffin-embedded primary and metastatic melanoma: frequency and distribution. J Cutan Pathol. 1998;25(4):204-209. (Pubitemid 28188031)
10. Jing X, Michael CW, Theoharis CG. The use of immunocytochemical study in the cytologic diagnosis of melanoma: evaluation of three antibodies. Diagn Cytopathol. 2013;41(2):126-130. Epub 2011 Oct 24.
11. King R, Weilbaecher KN, McGill G, et al. Microphthalmia transcription factor. A sensitive and specific melanocyte marker for MelanomaDiagnosis. Am J Pathol. 1999;155(3):731-738. (Pubitemid 29426819)
12. Orchard GE. 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. Histochem J. 2000;32(8):475-481.
13. Adema GJ, de Boer AJ, Vogel AM, et al. Molecular characterization of the melanocyte lineage-specific antigen gp100. J Biol Chem. 1994;269(31):20126- 20133. (Pubitemid 24250937)
14. Theos AC, Truschel ST, Raposo G, Marks MS. The Silver locus product Pmel17/gp100/Silv/ME20: controversial in name and in function. Pigment Cell Res. 2005;18(5):322-336. (Pubitemid 41360808)
15. Kwon BS, Halaban R, Ponnazhagan S, et al. Mouse silver mutation is caused by a single base insertion in the putative cytoplasmic domain of Pmel 17. Nucleic Acids Res. 1995;23(1):154-158.
16. Vennegoor C, Hageman P, Van Nouhuijs H, et al. A monoclonal antibody specific for cells of the melanocyte lineage. Am J Pathol. 1988;130(1):179-192. (Pubitemid 18044846)
17. Gown AM, Vogel AM, Hoak D, et al. Monoclonal antibodies specific for melanocytic tumors distinguish subpopulations of melanocytes. Am J Pathol. 1986;123(2):195-203. (Pubitemid 16072518)
18. 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(5):595-602. (Pubitemid 28213747)
19. Kaufmann O, Koch S, Burghardt J, et al. Tyrosinase, melan-A, and KBA62 as markers for the immunohistochemical identification of metastatic amelanotic melanomas on paraffin sections. Mod Pathol. 1998;11(8):740-746. (Pubitemid 28381608)
20. Gajjar NA, Cochran AJ, Binder SW. Is MAGE-1 expression in metastatic malignant melanomas really helpful? Am J Surg Pathol. 2004;28(7):883-888. (Pubitemid 38856843)
21. Miettinen M, Fernandez M, Franssila K, et al. Microphthalmia transcription factor in the immunohistochemical diagnosis of metastatic melanoma: comparison with four other melanoma markers. Am J Surg Pathol. 2001;25(2):205-211. (Pubitemid 32167502)
22. 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(12):583-589. (Pubitemid 32112965)
23. Mahmood MN, Lee MW, Linden MD, et al. Diagnostic value of HMB-45 and anti-Melan A staining of sentinel lymph nodes with isolated positive cells. Mod Pathol. 2002;15(12):1288-1293. (Pubitemid 35462996)
24. Granter SR, Weilbaecher KN, Quigley C, et al. Microphthalmia transcription factor: not a sensitive or specific marker for the diagnosis of desmoplastic melanoma and spindle cell (non-desmoplastic) melanoma. Am J Dermatopathol. 2001;23(3):185-189. (Pubitemid 32525406)
25. Chen YT, Stockert E, Jungbluth A, et al. Serological analysis of Melan-A(MART-1), a melanocyte-specific protein homogeneously expressed in human melanomas. Proc Natl Acad Sci U S A. 1996;93(12):5915-5919. (Pubitemid 26191318)
26. Coulie PG, Brichard V, Van Pel A, et al. A new gene coding for a differentiation antigen recognized by autologous cytolytic T lymphocytes on HLA-A2 melanomas. J Exp Med. 1994;180(1):35-42. (Pubitemid 24181053)
27. Kawakami Y, Eliyahu S, Delgado CH, et al. Identification of a human melanoma antigen recognized by tumor-infiltrating lymphocytes associated with in vivo tumor rejection. Proc Natl Acad Sci U S A. 1994;91(14):6458-6462.
28. De Maziere AM, Muehlethaler K, van Donselaar E, et al. The melanocytic protein Melan-A/MART-1 has a subcellular localization distinct from typical melanosomal proteins. Traffic. 2002;3(9):678-693.
29. Hoashi T, Watabe H, Muller J, et al. MART-1 is required for the function of the melanosomal matrix protein PMEL17/GP100 and the maturation of melanosomes. J Biol Chem. 2005;280(14):14006-14016. (Pubitemid 40517302)
30. Zalla MJ, Lim KK, Dicaudo DJ, Gagnot MM. Mohs micrographic excision of melanoma using immunostains. Dermatol Surg. 2000;26(8):771-784. (Pubitemid 30620524)
31. Albertini JG, Elston DM, Libow LF, et al. Mohs micrographic surgery for melanoma: a case series, a comparative study of immunostains, an informative case report, and a unique mapping technique. Dermatol Surg. 2002;28(8):656-665. (Pubitemid 34913271)
32. El Shabrawi-Caelen L, Kerl H, Cerroni L. Melan-A: not a helpful marker in distinction between melanoma in situ on sun-damaged skin and pigmented actinic keratosis. Am J Dermatopathol. 2004;26(5):364-366. (Pubitemid 39287355)
33. Beltraminelli H, Shabrawi-Caelen LE, Kerl H, Cerroni L. Melan-a-positive "pseudomelanocytic nests": a pitfall in the histopathologic and immunohistochemical diagnosis of pigmented lesions on sun-damaged skin. Am J Dermatopathol. 2009;31(3):305-308.
34. Raper HS. The Tyrosinase-tyrosine reaction: production from tyrosine of 5: 6-dihydroxyindole and 5: 6-dihydroxyindole-2-carboxylic acid-the precursors of melanin. Biochem J. 1927;21(1):89-96.
35. Theos AC, Tenza D, Martina JA, et al. Functions of adaptor protein (AP)-3 and AP-1 in tyrosinase sorting from endosomes to melanosomes. Mol Biol Cell. 2005;16(11):5356-5372. (Pubitemid 41566845)
36. Hodgkinson CA, Moore KJ, Nakayama A, et al. Mutations at the mouse microphthalmia locus are associated with defects in a gene encoding a novel basic-helix-loop-helix-zipper protein. Cell. 1993;74(2):395-404. (Pubitemid 23221714)
37. Du J, Miller AJ, Widlund HR, et al. MLANA/MART1 and SILV/PMEL17/GP100 are transcriptionally regulated by MITF in melanocytes and melanoma. Am J Pathol. 2003;163(1):333-343. (Pubitemid 36759618)
38. Tachibana M, Takeda K, Nobukuni Y, et al. Ectopic expression of MITF, a gene for waardenburg syndrome type 2, converts fibroblasts to cells with melanocyte characteristics. Nat Genet. 1996;14(1):50-54.
39. King R, Googe PB, Weilbaecher KN, et al. Microphthalmia transcription factor expression in cutaneous benign, malignant melanocytic, and nonmelanocytic tumors. Am J Surg Pathol. 2001;25(1):51-57. (Pubitemid 32001832)
40. 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(2):197-204. (Pubitemid 32167501)
41. Cochran AJ, Lu HF, Li PX, et al. S-100 protein remains a practical marker for melanocytic and other tumours. Melanoma Res. 1993;3(5):325-330. (Pubitemid 23329694)
42. Donato R, Cannon BR, Sorci G, et al. Functions of s100 proteins. Curr Mol Med. 2013;13(1):24-57.
43. Schultz ES, Diepgen TL, Von Den Driesch P. Clinical and prognostic relevance of serum S-100 beta protein in malignant melanoma. Br J Dermatol. 1998;138(3):426-430. (Pubitemid 28145509)
44. Wen DR, Bhuta S, Herschman HR, et al. S-100 protein: a marker for melanocytic tumors. Ann N Y Acad Sci. 1983;420:261-266. (Pubitemid 14147729)
45. Donato R. Intracellular and extracellular roles of S100 proteins. Microsc Res Tech. 2003;60(6):540-551.
46. Heizmann CW, Fritz G, Schafer BW. S100 proteins: structure, functions and pathology. Front Biosci. 2002;7:d1356-1368.
47. Donato R. Functional roles of S100 proteins, calcium-binding proteins of the eF-hand type. Biochim Biophys Acta. 1999;1450(3):191-231. (Pubitemid 29295473)
48. Donato R. S100: a multigenic family of calcium-modulated proteins of the eF-hand type with intracellular and extracellular functional roles. Int J Biochem Cell Biol. 2001;33(7):637-668. (Pubitemid 32520962)
49. Schafer BW, Heizmann CW. The S100 family of eF-hand calcium-binding proteins: functions and pathology. Trends Biochem Sci. 1996;21(4):134-140.
50. Zimmer DB, Cornwall EH, Landar A, Song W. The S100 protein family: history, function, and expression. Brain Res Bull. 1995;37(4):417-429.
51. Lin J, Yang Q, Wilder PT, et al. The calcium-binding protein S100B down-regulates p53 and apoptosis in malignant melanoma. J Biol Chem. 2010;285(35):27487-27498.
52. 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(3):196-200. (Pubitemid 32205039)
53. Nakajima T, Watanabe S, Sato Y, et al. An immunoperoxidase study of S-100 protein distribution in normal and neoplastic tissues. Am J Surg Pathol. 1982;6(8):715-727.
54. Kahn HJ, Marks A, Thom H, Baumal R. Role of antibody to S100 protein in diagnostic pathology. Am J Clin Pathol. 1983;79(3):341-347. (Pubitemid 13164114)
55. Morgan MB, Purohit C, Anglin TR. Immunohistochemical distinction of cutaneous spindle cell carcinoma. Am J Dermatopathol. 2008;30(3):228-232.
56. Busam KJ, Kucukgol D, Sato E, et al. Immunohistochemical analysis of novel monoclonal antibody PNL2 and comparison with other melanocyte differentiation markers. Am J Surg Pathol. 2005;29(3):400-406. (Pubitemid 40321977)
57. Trefzer U, Chen Y, Herberth G, et al. The monoclonal antibody SM5-1 recognizes a fibronectin variant which is widely expressed in melanoma. BMC Cancer. 2006;6:8.
58. Reinke S, Koniger P, Herberth G, et al. Differential expression of MART-1, tyrosinase, and SM5-1 in primary and metastatic melanoma. Am J Dermatopathol. 2005;27(5):401-406. (Pubitemid 41383293)
59. Campoli M, Ferrone S, Wang X. Functional and clinical relevance of chondroitin sulfate proteoglycan 4. Adv Cancer Res. 2010;109:73-121.
60. Natali PG, Giacomini P, Russo C, et al. Antigenic profile of human melanoma cells. Analysis with monoclonal antibodies to histocompatibility antigens and to melanoma-associated antigens. J Cutan Pathol. 1983;10(4):225-237. (Pubitemid 13073831)
61. Kageshita T, Kuriya N, Ono T, et al. Association of high molecular weight melanoma-associated antigen expression in primary acral lentiginous melanoma lesions with poor prognosis. Cancer Res. 1993;53(12):2830-2833. (Pubitemid 23180523)
62. Goto Y, Ferrone S, Arigami T, et al. Human high molecular weight-melanoma-associated antigen: utility for detection of metastatic melanoma in sentinel lymph nodes. Clin Cancer Res. 2008;14(11):3401-3407.
63. Goto Y, Arigami T, Murali R, et al. High molecular weight-melanoma- associated antigen as a biomarker of desmoplastic melanoma. Pigment Cell Melanoma Res. 2010;23(1):137-140.
64. Schmidt P, Kopecky C, Hombach A. Eradication of melanomas by targeted elimination of a minor subset of tumor cells. Proc Natl Acad Sci U S A. 2011;108(6):2474-2479.
65. Torisu-Itakura H, Schoellhammer HF, Sim MS, et al. Redirected lysis of human melanoma cells by a MCSP/CD3-bispecific BiTE antibody that engages patient-derived T cells. J Immunother. 2011;34(8):597-605.
66. Magro CM, Crowson AN, Desman G, Zippin JH. Soluble adenylyl cyclase antibody profile as a diagnostic adjunct in the assessment of pigmented lesions. Arch Dermatol. 2012;148(3):335-344. epub 2011 Nov 21.
67. Al Dhaybi R, Agoumi M, Gagne I, et al. p16 expression: a marker of differentiation between childhood malignant melanomas and Spitz nevi. J Am Acad Dermatol. 2011;65(2):357-363.
68. Hilliard NJ, Krahl D, Sellheyer K. p16 expression differentiates between desmoplastic Spitz nevus and desmoplastic melanoma. J Cutan Pathol. 2009;36(7):753-759.
69. George E, Polissar NL, Wick M. Immunohistochemical evaluation of p16INK4A, E-cadherin, and cyclin D1 expression in melanoma and Spitz tumors. Am J Clin Pathol. 2010;133(3):370-379.
70. Ohsie SJ, Sarantopoulos GP, Cochran AJ, Binder SW. Immunohistochemical characteristics of melanoma. J Cutan Pathol. 2008;35(5):433-444. (Pubitemid 351519417)
71. Bhawan J. Mel-5: a novel antibody for differential diagnosis of epidermal pigmented lesions of the skin in paraffin-embedded sections. Melanoma Res. 1997;7(1):43-48. (Pubitemid 27110281)
72. Bittner M, Meltzer P, Chen Y, et al. Molecular classification of cutaneous malignant melanoma by gene expression profiling. Nature. 2000;406(6795):536-540. (Pubitemid 30625740)
73. Lewis TB, Robison JE, Bastien R, et al. Molecular classification of melanoma using real-time quantitative reverse transcriptase-polymerase chain reaction. Cancer. 2005;104(8):1678-1686. (Pubitemid 41437431)
74. Wachsman W, Morhenn V, Palmer T, et al. Noninvasive genomic detection of melanoma. Br J Dermatol. 2011;164(4):797-806.
75. Gerami P, Li G, Pouryazdanparast P, et al. A highly specific and discriminatory FISH assay for distinguishing between benign and malignant melanocytic neoplasms. Am J Surg Pathol. 2012;36(6):808-817.
76. Gerami P, Jewell SS, Morrison LE, et al. Fluorescence in situ hybridization (FISH) as an ancillary diagnostic tool in the diagnosis of melanoma. Am J Surg Pathol. 2009;33(8):1146-1156.
77. Gerami P, Wass A, Mafee M, et al. Fluorescence in situ hybridization for distinguishing nevoid melanomas from mitotically active nevi. Am J Surg Pathol. 2009;33(12):1783-1788.
78. Vergier B, Prochazkova-Carlotti M, de la Fouchardiere A, et al. Fluorescence in situ hybridization, a diagnostic aid in ambiguous melanocytic tumors: european study of 113 cases. Mod Pathol. 2011;24(5):613-623.
79. Gaiser T, Kutzner H, Palmedo G, et al. Classifying ambiguous melanocytic lesions with FISH and correlation with clinical long-term follow up. Mod Pathol. 2010;23(3):413-419.
80. Raskin L, Ludgate M, Iyer RK, et al. Copy number variations and clinical outcome in atypical spitz tumors. Am J Surg Pathol. 2011;35(2):243-252.
81. Dalton SR, Gerami P, Kolaitis NA, et al. Use of fluorescence in situ hybridization (FISH) to distinguish intranodal nevus from metastatic melanoma. Am J Surg Pathol. 2012;34(2):231-237.
82. Gimotty PA, Elder DE, Fraker DL, et al. Identification of high-risk patients among those diagnosed with thin cutaneous melanomas. J Clin Oncol. 2007;25(9):1129-1134. (Pubitemid 46596766)
83. Thompson JF, Soong SJ, Balch CM, et al. Prognostic significance of mitotic rate in localized primary cutaneous melanoma: an analysis of patients in the multi-institutional American Joint Committee on Cancer melanoma staging database. J Clin Oncol. 2011;29(16):2199-2205.
84. Balch CM, Gershenwald JE, Soong SJ, et al. Final version of 2009 AJCC melanoma staging and classification. J Clin Oncol. 2009;27(36):6199-6206.
85. Vereecken P, Laporte M, Heenen M. Significance of cell kinetic parameters in the prognosis of malignant melanoma: a review. J Cutan Pathol. 2007;34(2):139-145. (Pubitemid 46145553)
86. Gimotty PA, Van Belle P, Elder DE, et al. Biologic and prognostic significance of dermal Ki67 expression, mitoses, and tumorigenicity in thin invasive cutaneous melanoma. J Clin Oncol. 2005;23(31):8048-8056. (Pubitemid 46657407)
87. Frahm SO, Schubert C, Parwaresch R, Rudolph P. High proliferative activity may predict early metastasis of thin melanomas. Hum Pathol. 2001;32(12):1376-1381.
88. Ladstein RG, Bachmann IM, Straume O, Akslen LA. Ki-67 expression is superior to mitotic count and novel proliferation markers PHH3, MCM4 and mitosin as a prognostic factor in thick cutaneous melanoma. BMC Cancer. 2010;10:140.
89. Barry M, Sinha SK, Leader MB, Kay EW. Poor agreement in recognition of abnormal mitoses: requirement for standardized and robust definitions. Histopathology. 2001;38(1):68-72. (Pubitemid 32126191)
90. Kruper LL, Spitz FR, Czerniecki BJ, et al. Predicting sentinel node status in AJCC stage I/II primary cutaneous melanoma. Cancer. 2006;107(10):2436-2445. (Pubitemid 44748527)
91. Balch CM, Gershenwald JE, Soong SJ, et al. Multivariate analysis of prognostic factors among 2,313 patients with stage III melanoma: comparison of nodal micrometastases versus macrometastases. J Clin Oncol. 2010;28(14):2452- 2459.
92. Davies H, Bignell GR, Cox C, et al. Mutations of the BRAF gene in human cancer. Nature. 2002;417(6892):949-954. (Pubitemid 34716871)
93. Shinozaki M, Fujimoto A, Morton DL, Hoon DS. Incidence of BRAF oncogene mutation and clinical relevance for primary cutaneous melanomas. Clin Cancer Res. 2004;10(5):1753-1757. (Pubitemid 38435567)
94. Curtin JA, Fridlyand J, Kageshita T, et al. Distinct sets of genetic alterations in melanoma. N Engl J Med. 2005;353(20):2135-2147. (Pubitemid 41653105)
95. Akslen LA, Angelini S, Straume O, et al. BRAF and NRAS mutations are frequent in nodular melanoma but are not associated with tumor cell proliferation or patient survival. J Invest Dermatol. 2005;125(2):312-317. (Pubitemid 41648165)
96. Mintz-Weber CS, Johnson JP. Identification of the elements regulating the expression of the cell adhesion molecule MCAM/MUC18. Loss of AP-2 is not required for MCAM expression in melanoma cell lines. J Biol Chem. 2000;275(44): 34672-34680.
97. Bar-Eli M. Role of AP-2 in tumor growth and metastasis of human melanoma. Cancer Metastasis Rev. 1999;18(3):377-385. (Pubitemid 30104070)
98. Rummel MM, Sers C, Johnson JP. Phorbol ester and cyclic AMP-mediated regulation of the melanoma-associated cell adhesion molecule MUC18/MCAM. Cancer Res. 1996;56(9):2218-2223.
99. Shih LM, Hsu MY, Palazzo JP, Herlyn M. The cell-cell adhesion receptor Mel-CAM acts as a tumor suppressor in breast carcinoma. Am J Pathol. 1997;151(3):745-751. (Pubitemid 27385606)
100. Pearl RA, Pacifico MD, Richman PI, Wilson GD, Grover R. Stratification of patients by melanoma cell adhesion molecule (MCAM) expression on the basis of risk: implications for sentinel lymph node biopsy. J Plast Reconstr Aesthet Surg. 2008;61(3):265-271. (Pubitemid 351215133)
101. Pacifico MD, Grover R, Richman PI, et al. Development of a tissue array for primary melanoma with long-term follow-up: discovering melanoma cell adhesion molecule as an important prognostic marker. Plast Reconstr Surg. 2005;115(2):367-375. (Pubitemid 40279292)
102. Thirumoorthy N, Shyam Sunder A, Manisenthil Kumar K, et al. A review of metallothionein isoforms and their role in pathophysiology. World J Surg Oncol. 2011;9:54.
103. Emri E, Egervari K, Varvolgyi T, et al. Correlation among metallothionein expression, intratumoural macrophage infiltration and the risk of metastasis inhuman cutaneous malignant melanoma. J Eur Acad Dermatol Venereol. 2012.
104. Weinlich G, Topar G, Eisendle K, et al. Comparison of metallothionein-overexpression with sentinel lymph node biopsy as prognostic factors in melanoma. J Eur Acad Dermatol Venereol. 2007;21(5):669-677. (Pubitemid 46916766)
105. Weinlich G, Eisendle K, Hassler E, et al. Metallothionein - overexpression as a highly significant prognostic factor in melanoma: a prospective study on 1270 patients. Br J Cancer. 2006;94(6):835-841.
106. Bilalovic N, Sandstad B, Golouh E, et al. CD10 protein expression in tumor and stromal cells of malignant melanoma is associated with tumor progression. Mod Pathol. 2004;17(10):1251-1258. (Pubitemid 39312951)
107. Oba J, Nakahara T, Hayashida S, et al. Expression of CD10 predicts tumor progression and unfavorable prognosis in malignant melanoma. J Am Acad Dermatol. 2011;65(6): 1152-1160.
108. Bertucci F, Pages C, Finetti P, et al. Gene expression profiling of human melanoma cell lines with distinct metastatic potential identifies new progression markers. Anticancer Res. 2007;27(5A):3441-3449. (Pubitemid 47607574)
109. Horvat S, Mlinaric-Majerski K, Glavas-Obrovac L, et al. Tumor-cell-targeted methionine-enkephalin analogues containing unnatural amino acids: design, synthesis, and in vitro antitumor activity. J Med Chem. 2006;49(11):3136-3142. (Pubitemid 43830512)
110. Manske JM, Hanson SE. Substance-P-mediated immunomodulation of tumor growth in a murine model. Neuroimmunomodulation. 2005;12(4):201-210. (Pubitemid 40910973)
111. Gould Rothberg Be, Bracken MB, Rimm DL. Tissue biomarkers for prognosis in cutaneous melanoma: a systematic review and meta-analysis. J Natl Cancer Inst. 2009;101(7):452-474.
112. Gould Rothberg BE, Rimm DL. Biomarkers: the useful and the not so useful - an assessment of molecular prognostic markers for cutaneous melanoma. J Invest Dermatol. 2010;130(8): 1971-1987.
113. Lin H, Wong RP, Martinka M, Li G. Loss of SNF5 expression correlates with poor patient survival in melanoma. Clin Cancer Res. 2009;15(20):6404-6411.
114. Haqq C, Nosrati M, Sudilovsky D, et al. The gene expression signatures of melanoma progression. Proc Natl Acad Sci U S A. 2005;102(17):6092-6097. (Pubitemid 40594260)
115. Winnepenninckx V, Lazar V, Michiels S, et al. Gene expression profiling of primary cutaneous melanoma and clinical outcome. J Natl Cancer Inst. 2006;98(7):472-482.
116. Journe F, Id Boufker H, Van Kempen L, et al. TYrP1 mrNA expression in melanoma metastases correlates with clinical outcome. Br J Cancer. 2011;105(11):1726-1732.
117. Conway C, Mitra A, Jewell R, et al. Gene expression profiling of paraffin-embedded primary melanoma using the DASL assay identifies increased osteopontin expression as predictive of reduced relapse-free survival. Clin Cancer Res. 2009;15(22): 6939-6946.
118. Alonso SR, Ortiz P, Pollan M, et al. Progression in cutaneous malignant melanoma is associated with distinct expression profiles: a tissue microarray-based study. Am J Pathol. 2004;164(1):193-203. (Pubitemid 38364604)
119. Kashani-Sabet M, Venna S, Nosrati M, et al. A multimarker prognostic assay for primary cutaneous melanoma. Clin Cancer Res. 2009;15(22):6987-6992.
120. Gould Rothberg BE, Berger AJ, Molinaro AM, et al. Melanoma prognostic model using tissue microarrays and genetic algorithms. J Clin Oncol. 2009;27(34):5772-5780.
121. Koh SS, Wei JP, Li X, et al. Differential gene expression profiling of primary cutaneous melanoma and sentinel lymph node metastases. Mod Pathol. 2012;25(6):828-837. epub 2012 Mar 9.
122. Jonsson G, Busch C, Knappskog S, et al. Gene expression profiling-based identification of molecular subtypes in stage IV melanomas with different clinical outcome. Clin Cancer Res. 2010;16(13):3356-3367.
123. North JP, Vetto JT, Murali R, et al. Assessment of copy number status of chromosomes 6 and 11 by FISH provides independent prognostic information in primary melanoma. Am J Surg Pathol. 2011;35(8):1146-1150.
124. Gerami P, Jewell SS, Pouryazdanparast P, et al. Copy number gains in 11q13 and 8q24 [corrected] are highly linked to prognosis in cutaneous malignant melanoma. J Mol Diagn. 2011;13(3):352-358.
125. Brochez L, Naeyaert JM. Serological markers for melanoma. Br J Dermatol. 2000;143(2):256-268. (Pubitemid 30650391)
126. Agarwala SS, Keilholz U, Gilles E, et al. LDH correlation with survival in advanced melanoma from two large, randomised trials (Oblimersen GM301 and eOrTC 18951). Eur J Cancer. 2009;45(10):1807-1814.
127. Koukourakis MI, Giatromanolaki A, Sivridis E, et al. Lactate dehydrogenase-5 (LDH-5) overexpression in non-small-cell lung cancer tissues is linked to tumour hypoxia, angiogenic factor production and poor prognosis. Br J Cancer. 2003;89(5): 877-885. (Pubitemid 37175811)
128. Finck SJ, Giuliano AE, Morton DL. LDH and melanoma. Cancer. 1983;51(5):840-843. (Pubitemid 13143161)
129. Deichmann M, Benner A, Bock M, et al. S100-Beta, melanoma-inhibiting activity, and lactate dehydrogenase discriminate progressive from nonprogressive American Joint Committee on Cancer stage IV melanoma. J Clin Oncol. Jun 1999;17(6):1891-1896. (Pubitemid 29269262)
130. Sirott MN, Bajorin DF, Wong GY, et al. Prognostic factors in patients with metastatic malignant melanoma. A multivariate analysis. Cancer. 1993;72(10):3091-3098. (Pubitemid 23335058)
131. weide B, Elsasser M, Buttner P, et al. Serum markers lactate dehydrogenase and S100B predict independently disease outcome in melanoma patients with distant metastasis. Br J Cancer. 2012;107(3):422-428.
132. Egberts F, Hitschler WN, Weichenthal M, Hauschild A. Prospective monitoring of adjuvant treatment in high-risk melanoma patients: lactate dehydrogenase and protein S-100B as indicators of relapse. Melanoma Res. 2009;19(1):31-35.
133. Kaskel P, Berking C, Sander S, et al. S-100 protein in peripheral blood: a marker for melanoma metastases: a prospective 2-center study of 570 patients with melanoma. J Am Acad Dermatol. 1999;41(6):962-969.
134. Bottoni U, Izzo P, Richetta A, et al. S100 serum level: a tumour marker for metastatic melanoma. Melanoma res. 2003;13(4):427-429. (Pubitemid 36900707)
135. Kruijff S, Bastiaannet E, Brouwers AH, et al. Use of S-100B to evaluate therapy effects during bevacizumab induction treatment in AJCC stage III melanoma. Ann Surg Oncol. 2012;19(2): 620-626.
136. Hauschild A, Engel G, Brenner W, et al. S100B protein detection in serum is a significant prognostic factor in metastatic melanoma. Oncology. 1999;56(4):338-344. (Pubitemid 29240361)
137. Martenson ED, Hansson LO, Nilsson B, et al. Serum S-100b protein as a prognostic marker in malignant cutaneous melanoma. J Clin Oncol. 2001;19(3):824-831. (Pubitemid 32119098)
138. Tarhini AA, Stuckert J, Lee S, et al. Prognostic significance of serum S100B protein in high-risk surgically resected melanoma patients participating in Intergroup Trial eCOG 1694. J Clin Oncol. 2009;27(1):38-44.
139. Bolander A, Agnarsdottir M, Wagenius G, et al. Serological and immunohistochemical analysis of S100 and new derivatives as markers for prognosis in patients with malignant melanoma. Melanoma Res. 2008;18(6):412-419.
140. Mocellin S, Zavagno G, Nitti D. The prognostic value of serum S100B in patients with cutaneous melanoma: a meta-analysis. Int J Cancer. 2008;123(10):2370-2376.
141. Kruijff S, Bastiaannet E, Kobold AC. S-100B concentrations predict disease-free survival in stage III melanoma patients. Ann Surg Oncol. 2009;16(12):3455-3462.
142. Banfalvi T, Boldizsar M, Gergye M, et al. Comparison of prognostic significance of serum 5-S-Cysteinyldopa, LDH and S-100B protein in Stage III-IV malignant melanoma. Pathol Oncol Res. 2002;8(3):183-187. (Pubitemid 35407638)
143. Krahn G, Kaskel P, Sander S, et al. S100 beta is a more reliable tumor marker in peripheral blood for patients with newly occurred melanoma metastases compared with MIA, albumin and lactate-dehydrogenase. Anticancer Res. 2001;21(2B): 1311-1316. (Pubitemid 32494139)
144. Hamberg AP, Korse CM, Bonfrer JM, de Gast GC. Serum S100B is suitable for prediction and monitoring of response to chemoimmunotherapy in metastatic malignant melanoma. Melanoma Res. 2003;13(1):45-49. (Pubitemid 36269813)
145. Fagnart OC, Sindic CJ, Laterre C. Particle counting immunoassay of S100 protein in serum. Possible relevance in tumors and ischemic disorders of the central nervous system. Clin Chem. 1988;34(7):1387-1391.
146. Thompson D, Pepys MB, wood SP. The physiological structure of human C-reactive protein and its complex with phosphocholine. Structure. 1999;7(2):169-177. (Pubitemid 29159702)
147. Pepys MB, Hirschfield GM. C-reactive protein: a critical update. J Clin Invest. 2003;111(12):1805-1812. (Pubitemid 38057722)
148. Castell JV, Gomez-Lechon MJ, David M, et al. Interleukin-6 is the major regulator of acute phase protein synthesis in adult human hepatocytes. FEBS Lett. 1989;242(2):237-239. (Pubitemid 19020112)
149. Moshage HJ, Roelofs HM, van Pelt JF, et al. The effect of interleukin-1, interleukin-6 and its interrelationship on the synthesis of serum amyloid A and C-reactive protein in primary cultures of adult human hepatocytes. Biochem Biophys Res Commun. 1988;155(1):112-117.
150. Allin KH, Nordestgaard BG. Elevated C-reactive protein in the diagnosis, prognosis, and cause of cancer. Crit Rev Clin Lab Sci. 2011;48(4):155-170.
151. Deichmann M, Benner A, Waldmann V, et al. Interleukin-6 and its surrogate C-reactive protein are useful serum markers for monitoring metastasized malignant melanoma. J Exp Clin Cancer Res. 2000;19(3):301-307.
152. Mouawad R, Benhammouda A, Rixe O, et al. Endogenous interleukin 6 levels in patients with metastatic malignant melanoma: correlation with tumor burden. Clin Cancer Res. 1996;2(8):1405-1409. (Pubitemid 26299441)
153. Deichmann M, Kahle B, Moser K, et al. Diagnosing melanoma patients entering American Joint Committee on Cancer stage IV, C-reactive protein in serum is superior to lactate dehydrogenase. Br J Cancer. 2004;91(4):699-702. (Pubitemid 39141627)
154. Tartour e, Blay JY, Dorval T, et al. Predictors of clinical response to interleukin-2 - based immunotherapy in melanoma patients: a French multiinstitutional study. J Clin Oncol. 1996;14(5): 1697-1703.
155. Bogdahn U, Apfel R, Hahn M, et al. Autocrine tumor cell growth-inhibiting activities from human malignant melanoma. Cancer Res. 1989;49(19):5358-5363. (Pubitemid 19240474)
156. Guba M, Bosserhoff AK, Steinbauer M, et al. Overexpression of melanoma inhibitory activity (MIA) enhances extravasation and metastasis of A-mel 3 melanoma cells in vivo. Br J Cancer. 2000;83(9):1216-1222.
157. Bosserhoff AK, Hein R, Bogdahn U, Buettner R. Structure and promoter analysis of the gene encoding the human melanoma-inhibiting protein MIA. J Biol Chem. 1996;271(1):490-495.
158. Deichmann M, Benner A, Kuner N, et al. Are responses to therapy of metastasized malignant melanoma reflected by decreasing serum values of S100beta or melanoma inhibitory activity (MIA)? Melanoma Res. Jun 2001;11(3):291-296. (Pubitemid 32578816)
159. Cao MG, Auge JM, Molina R, et al. Melanoma inhibiting activity protein (MIA), beta-2 microglobulin and lactate dehydrogenase (LDH) in metastatic melanoma. Anticancer Res. 2007;27(1B):595-599. (Pubitemid 46374982)
160. Bosserhoff AK, Kaufmann M, Kaluza B, et al. Melanoma-inhibiting activity, a novel serum marker for progression of malignant melanoma. Cancer Res. 1997;57(15):3149-3153. (Pubitemid 27351728)
161. Meral R, Duranyildiz D, Tas F, et al. Prognostic significance of melanoma inhibiting activity levels in malignant melanoma. Melanoma Res. 2001;11(6):627-632. (Pubitemid 33152354)
162. Stahlecker J, Gauger A, Bosserhoff A, et al. MIA as a reliable tumor marker in the serum of patients with malignant melanoma. Anticancer Res. 2000;20(6D):5041-5044. (Pubitemid 32319076)
163. Bosserhoff AK, Kuster H, Hein R. Elevated MIA levels in the serum of pregnant women and of children. Clin Exp Dermatol. 2004;29(6):628-629. (Pubitemid 39573653)
164. Sasahira T, Kirita T, Kurihara M, et al. MIA-dependent angiogenesis and lymphangiogenesis are closely associated with progression, nodal metastasis and poor prognosis in tongue squamous cell carcinoma. Eur J Cancer. 2010;46(12):2285-2294.
165. Connolly DT, Heuvelman DM, Nelson R, et al. Tumor vascular permeability factor stimulates endothelial cell growth and angiogenesis. J Clin Invest. 1989;84(5):1470-1478. (Pubitemid 19272234)
166. Folkman J. What is the evidence that tumors are angiogenesis dependent? J Natl Cancer Inst. 1990;82(1):4-6. (Pubitemid 20020880)
167. Redondo P, Sanchez-Carpintero I, Bauza A, et al. Immunologic escape and angiogenesis in human malignant melanoma. J Am Acad Dermatol. 2003;49(2):255-263. (Pubitemid 36951274)
168. Freeman Mr, Schneck FX, Gagnon ML, et al. Peripheral blood T lymphocytes and lymphocytes infiltrating human cancers express vascular endothelial growth factor: a potential role for T cells in angiogenesis. Cancer Res. 1995;55(18):4140-4145.
169. Shellman YG, Park YL, Marr DG, et al. Release of vascular endothelial growth factor from a human melanoma cell line, wM35, is induced by hypoxia but not ultraviolet radiation and is potentiated by activated ras mutation. J Invest Dermatol. 2003;121(4):910-917. (Pubitemid 37239138)
170. Wartiovaara U, Salven P, Mikkola H, et al. Peripheral blood platelets express VeGF-C and VeGF which are released during platelet activation. Thromb Haemost. 1998;80(1):171-175. (Pubitemid 28353517)
171. Ugurel S, Rappl G, Tilgen W, Reinhold U. Increased serum concentration of angiogenic factors in malignant melanoma patients correlates with tumor progression and survival. J Clin Oncol. 2001;19(2):577-583. (Pubitemid 32112873)
172. Redondo P, Bandres E, Solano T, Okroujnov I, Garcia-Foncillas J. Vascular endothelial growth factor (VeGF) and melanoma. N-acetylcysteine downregulates VeGF production in vitro. Cytokine. 2000;12(4):374-378. (Pubitemid 30449829)
173. Pelletier F, Bermont L, Puzenat e, et al. Circulating vascular endothelial growth factor in cutaneous malignant melanoma. Br J Dermatol. 2005;152(4):685-689. (Pubitemid 40571300)
174. Osella-Abate S, Quaglino P, Savoia P, et al. VeGF-165 serum levels and tyrosinase expression in melanoma patients: correlation with the clinical course. Melanoma Res. 2002;12(4):325-334. (Pubitemid 34816437)
175. Viac J, Schmitt D, Claudy A. Circulating vascular endothelial growth factor (VeGF) is not a prognostic indicator in malignant melanoma. Cancer Lett. 1998;125(1-2):35-38. (Pubitemid 28151906)
176. VanGuilder HD, Vrana KE, Freeman WM. Twenty-five years of quantitative PCr for gene expression analysis. Biotechniques. 2008;44(5):619-626. (Pubitemid 351656280)
177. Smith B, Selby P, Southgate J, et al. Detection of melanoma cells in peripheral blood by means of reverse transcriptase and polymerase chain reaction. Lancet. 1991;338(8777):1227-1229.
178. Arenberger P, Arenbergerova M, Vohradnikova O, Kremen J. Early detection of melanoma progression by quantitative real-time rT-PCr analysis for multiple melanoma markers. Keio J Med. 2008;57(1):57-64. (Pubitemid 351744047)
179. Koyanagi K, Kuo C, Nakagawa T, et al. Multimarker quantitative real-time PCr detection of circulating melanoma cells in peripheral blood: relation to disease stage in melanoma patients. Clin Chem. 2005;51(6):981-988. (Pubitemid 40740878)
180. Mocellin S, Del Fiore P, Guarnieri L, et al. Molecular detection of circulating tumor cells is an independent prognostic factor in patients with high-risk cutaneous melanoma. Int J Cancer. 2004;111(5):741-745. (Pubitemid 39062897)
181. Palmieri G, Ascierto PA, Perrone F, et al. Prognostic value of circulating melanoma cells detected by reverse transcriptase-polymerase chain reaction. J Clin Oncol. 2003;21(5):767-773. (Pubitemid 46606433)
182. Raso A, Mascelli S, Nozza P, et al. Detection of transplacental melanoma metastasis using quantitative PCr. Diagn Mol Pathol. 2010;19(2):78-82.
183. Daniotti M, Vallacchi V, Rivoltini L, et al. Detection of mutated BrAFV600e variant in circulating DNA of stage III-IV melanoma patients. Int J Cancer. 2007;120(11):2439-2444. (Pubitemid 46642132)
184. Pinzani P, Salvianti F, Cascella R, et al. Allele specific Taqman-based real-time PCr assay to quantify circulating BrAFV600e mutated DNA in plasma of melanoma patients. Clin Chim Acta. 2010;411(17-18):1319-1324.
185. Esteller M. Non-coding RNAs in human disease. Nat Rev Genet. 2011;12(12):861-874.
186. Kasinski AL, Slack FJ. epigenetics and genetics. MicroRNAs en route to the clinic: progress in validating and targeting microRNAs for cancer therapy. Nat Rev Cancer. 2011;11(12): 849-864.
187. Sandhu S, Garzon R. Potential applications of microRNAs in cancer diagnosis, prognosis, and treatment. Semin Oncol. 2011;38(6):781-787.
188. Caramuta S, Egyhazi S, Rodolfo M, et al. MicroRNA expression profiles associated with mutational status and survival in malignant melanoma. J Invest Dermatol. 2010;130(8):2062-2070.
189. Luo C, Tetteh PW, Merz PR, et al. miR-137 Inhibits the Invasion of Melanoma Cells through Downregulation of Multiple Oncogenic Target Genes. J Invest Dermatol. 2013;133(3):768-775.
190. Mueller DW, Rehli M, Bosserhoff AK. miRNA expression profiling in melanocytes and melanoma cell lines reveals miRNAs associated with formation and progression of malignant melanoma. J Invest Dermatol. 2009;129(7):1740-1751.
191. Xu Y, Brenn T, Brown ER, Doherty V, Melton DW. Differential expression of microRNAs during melanoma progression: miR-200c, miR-205 and miR-211 are downregulated in melanoma and act as tumour suppressors. Br J Cancer. 2012;106(3):553-561.
192. Kosaka N, Iguchi H, Ochiya T. Circulating microRNA in body fluid: a new potential biomarker for cancer diagnosis and prognosis. Cancer Sci. 2010;101(10):2087-2092.
193. Palmer SR, Erickson LA, Ichetovkin I, et al. Circulating serologic and molecular biomarkers in malignant melanoma. Mayo Clin Proc. 2011;86(10):981-990.
194. Grichnik JM. Melanoma, nevogenesis, and stem cell biology. J Invest Dermatol. 2008;128(10):2365-2380.