Skip to main content

Advertisement

Log in

Progression of cutaneous melanoma: implications for treatment

  • Research Paper
  • Published:
Clinical & Experimental Metastasis Aims and scope Submit manuscript

An Erratum to this article was published on 03 October 2012

Abstract

The survival rates of melanoma, like any type of cancer, become worse with advancing stage. Spectrum theory is most consistent with the progression of melanoma from the primary site to the in-transit locations, regional or sentinel lymph nodes and beyond to the distant sites. Therefore, early diagnosis and surgical treatment before its spread is the most effective treatment. Recently, new approaches have revolutionized the diagnosis and treatment of melanoma. Genomic profiling and sequencing will form the basis for molecular taxonomy for more accurate subgrouping of melanoma patients in the future. New insights of molecular mechanisms of metastasis are summarized in this review article. Sentinel lymph node biopsy has become a standard of care for staging primary melanoma without the need for a more morbid complete regional lymph node dissection. With recent developments in molecular biology and genomics, novel molecular targeted therapy is being developed through clinical trials.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. Murphy MJ (2012) Diagnostic and prognostic biomarkers and therapeutic targets in melanoma. Springer, New York

    Book  Google Scholar 

  2. Becker D, Mihm MC, Hewitt SM et al (2006) Markers and tissue resources for melanoma: meeting report. Cancer Res 66:10652–10657

    Article  PubMed  CAS  Google Scholar 

  3. Beecher C (2003) The human metabolome. In: Harrigan G, Goodacre R (eds) Metabolic profilings: its role in biomarker discovery and gene function analysis. Kluwer Academic Publishers, Boston, pp 311–319

    Chapter  Google Scholar 

  4. Flaherty KT (2011) BRAF inhibitors and melanoma. Cancer J 17:505–511

    Article  PubMed  CAS  Google Scholar 

  5. Balch CM, Gershenwald JE, Soong SJ et al (2009) Final version of 2009 AJCC melanoma staging and classification. J Clin Oncol 27:6199–6206

    Article  PubMed  Google Scholar 

  6. Leong SP, Gershenwald JE, Soong SJ et al (2011) Cutaneous melanoma: a model to study cancer metastasis. J Surg Oncol 103:538–549

    Article  PubMed  Google Scholar 

  7. Raz A, Ben-Ze’ev A (1983) Modulation of the metastatic capability in B16 melanoma by cell shape. Science 221:1307–1310

    Article  PubMed  CAS  Google Scholar 

  8. Gupta GP, Massague J (2006) Cancer metastasis: building a framework. Cell 127:679–695

    Article  PubMed  CAS  Google Scholar 

  9. Valastyan S, Weinberg RA (2011) Tumor metastasis: molecular insights and evolving paradigms. Cell 147:275–292

    Article  PubMed  CAS  Google Scholar 

  10. Damsky WE, Curley DP, Santhanakrishnan M et al (2011) beta-catenin signaling controls metastasis in Braf-activated Pten-deficient melanomas. Cancer Cell 20:741–754

    Article  PubMed  CAS  Google Scholar 

  11. Fidler IJ (2003) The pathogenesis of cancer metastasis: the ‘seed and soil’ hypothesis revisited. Nat Rev Cancer 3:453–458

    Article  PubMed  CAS  Google Scholar 

  12. Bogenrieder T, Herlyn M (2003) Axis of evil: molecular mechanisms of cancer metastasis. Oncogene 22:6524–6536

    Article  PubMed  CAS  Google Scholar 

  13. Mortarini R, Gismondi A, Maggioni A et al (1995) Mitogenic activity of laminin on human melanoma and melanocytes: different signal requirements and role of beta 1 integrins. Cancer Res 55:4702–4710

    PubMed  CAS  Google Scholar 

  14. Kalluri R, Weinberg RA (2009) The basics of epithelial-mesenchymal transition. J Clin Invest 119:1420–1428

    Article  PubMed  CAS  Google Scholar 

  15. Scheel C, Weinberg RA (2011) Phenotypic plasticity and epithelial-mesenchymal transitions in cancer and normal stem cells? Int J Cancer 129:2310–2314

    Article  PubMed  CAS  Google Scholar 

  16. Ma J, Lin JY, Alloo A et al (2010) Isolation of tumorigenic circulating melanoma cells. Biochem Biophys Res Commun 402:711–717

    Article  PubMed  CAS  Google Scholar 

  17. Maldonado JL, Fridlyand J, Patel H et al (2003) Determinants of BRAF mutations in primary melanomas. J Natl Cancer Inst 95:1878–1890

    Article  PubMed  CAS  Google Scholar 

  18. Curtin JA, Busam K, Pinkel D et al (2006) Somatic activation of KIT in distinct subtypes of melanoma. J Clin Oncol 24:4340–4346

    Article  PubMed  CAS  Google Scholar 

  19. Bouffard D, Duncan LM, Howard CA et al (1994) Actin-binding protein expression in benign and malignant melanocytic proliferations. Hum Pathol 25:709–714

    Article  PubMed  CAS  Google Scholar 

  20. Van Belle PA, Elenitsas R, Satyamoorthy K et al (1999) Progression-related expression of beta3 integrin in melanomas and nevi. Hum Pathol 30:562–567

    Article  PubMed  Google Scholar 

  21. Saalbach A, Wetzel A, Haustein UF et al (2005) Interaction of human Thy-1 (CD 90) with the integrin alphavbeta3 (CD51/CD61): an important mechanism mediating melanoma cell adhesion to activated endothelium. Oncogene 24:4710–4720

    Article  PubMed  CAS  Google Scholar 

  22. Hofmann UB, Westphal JR, Waas ET et al (1999) Matrix metalloproteinases in human melanoma cell lines and xenografts: increased expression of activated matrix metalloproteinase-2 (MMP-2) correlates with melanoma progression. Br J Cancer 81:774–782

    Article  PubMed  CAS  Google Scholar 

  23. Bodey B, Bodey B Jr, Siegel SE et al (2001) Matrix metalloproteinase expression in malignant melanomas: tumor-extracellular matrix interactions in invasion and metastasis. In Vivo (Athens, Greece) 15:57–64

    CAS  Google Scholar 

  24. Chen Y, Huang L, Yu J (2012) Evaluation of heparanase and matrix metalloproteinase-9 in patients with cutaneous malignant melanoma. J Dermatol 39:339–343

    Article  PubMed  CAS  Google Scholar 

  25. Das SK, Bhutia SK, Kegelman TP et al (2012) MDA-9/syntenin: a positive gatekeeper of melanoma metastasis. Front Biosci 17:1–15

    Article  PubMed  CAS  Google Scholar 

  26. Lu Z, Lu N, Li C et al (2012) Oroxylin A inhibits matrix metalloproteinase-2/9 expression and activation by up-regulating tissue inhibitor of metalloproteinase-2 and suppressing the ERK1/2 signaling pathway. Toxicol Lett 209:211–220

    Article  PubMed  CAS  Google Scholar 

  27. Kim M, Gans JD, Nogueira C et al (2006) Comparative oncogenomics identifies NEDD9 as a melanoma metastasis gene. Cell 125:1269–1281

    Article  PubMed  CAS  Google Scholar 

  28. Girouard SD, Laga AC, Mihm MC et al (2012) SOX2 contributes to melanoma cell invasion. Lab Investig 92:362–370

    Article  PubMed  CAS  Google Scholar 

  29. Laga AC, Zhan Q, Weishaupt C et al (2011) SOX2 and nestin expression in human melanoma: an immunohistochemical and experimental study. Exp Dermatol 20:339–345

    Article  PubMed  CAS  Google Scholar 

  30. Laga AC, Lai CY, Zhan Q et al (2010) Expression of the embryonic stem cell transcription factor SOX2 in human skin: relevance to melanocyte and merkel cell biology. Am J Pathol 176:903–913

    Article  PubMed  CAS  Google Scholar 

  31. Ruiter D, Bogenrieder T, Elder D et al (2002) Melanoma-stroma interactions: structural and functional aspects. Lancet Oncol 3:35–43

    Article  PubMed  CAS  Google Scholar 

  32. Zigrino P, Kuhn I, Bauerle T et al (2009) Stromal expression of MMP-13 is required for melanoma invasion and metastasis. J Investig Dermatol 129:2686–2693

    Article  PubMed  CAS  Google Scholar 

  33. Hoffmann C, Horst HA, Weichenthal M et al (2005) Malignant melanoma and HIV infection—aggressive course despite immune reconstitution. Onkologie 28:35–37

    Article  PubMed  Google Scholar 

  34. Navab R, Strumpf D, Bandarchi B et al (2011) Prognostic gene-expression signature of carcinoma-associated fibroblasts in non-small cell lung cancer. Proc Natl Acad Sci USA 108:7160–7165

    Article  PubMed  CAS  Google Scholar 

  35. Navab R, Liu J, Seiden-Long I et al (2009) Co-overexpression of Met and hepatocyte growth factor promotes systemic metastasis in NCI-H460 non-small cell lung carcinoma cells. Neoplasia 11:1292–1300

    PubMed  CAS  Google Scholar 

  36. Chiang AC, Massague J (2008) Molecular basis of metastasis. N Engl J Med 359:2814–2823

    Article  PubMed  CAS  Google Scholar 

  37. Gupta GP, Perk J, Acharyya S et al (2007) ID genes mediate tumor reinitiation during breast cancer lung metastasis. Proc Natl Acad Sci USA 104:19506–19511

    Article  PubMed  CAS  Google Scholar 

  38. Swarbrick A, Roy E, Allen T et al (2008) Id1 cooperates with oncogenic Ras to induce metastatic mammary carcinoma by subversion of the cellular senescence response. Proc Natl Acad Sci USA 105:5402–5407

    Article  PubMed  CAS  Google Scholar 

  39. Kaplan RN, Riba RD, Zacharoulis S et al (2005) VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche. Nature 438:820–827

    Article  PubMed  CAS  Google Scholar 

  40. Mihm MC Jr, Nelson JS (2010) Hypothesis: the metastatic niche theory can elucidate infantile hemangioma development. J Cutan Pathol 37(Suppl 1):83–87

    Article  PubMed  Google Scholar 

  41. Li F, Tiede B, Massague J et al (2007) Beyond tumorigenesis: cancer stem cells in metastasis. Cell Res 17:3–14

    Article  PubMed  CAS  Google Scholar 

  42. Damsky WE, Rosenbaum LE, Bosenberg M (2011) Decoding melanoma metastasis. Cancers 3(1):126–163

    Article  Google Scholar 

  43. Youngs SJ, Ali SA, Taub DD et al (1997) Chemokines induce migrational responses in human breast carcinoma cell lines. Int J Cancer 71:257–266

    Article  PubMed  CAS  Google Scholar 

  44. Shu S, Cochran AJ, Huang RR et al (2006) Immune responses in the draining lymph nodes against cancer: implications for immunotherapy. Cancer Metastasis Rev 25:233–242

    Article  PubMed  Google Scholar 

  45. Hoon DS, Kitago M, Kim J et al (2006) Molecular mechanisms of metastasis. Cancer Metastasis Rev 25:203–220

    Article  PubMed  CAS  Google Scholar 

  46. Kawada K, Sonoshita M, Sakashita H et al (2004) Pivotal role of CXCR3 in melanoma cell metastasis to lymph nodes. Cancer Res 64:4010–4017

    Article  PubMed  CAS  Google Scholar 

  47. Greenberg ES, Chong KK, Huynh KT, Tanaka R, Hoon DS (2012) Epigenetic biomarkers in skin cancer. Cancer Lett. doi:10.1016\j.canlet.2010.01.020

  48. Hoshimoto S, Kuo CT, Chong KK et al (2012) AIM1 and LINE-1 epigenetic aberrations in tumor and serum relate to melanoma progression and disease outcome. J Investig Dermatol 132:1689–1697

    Article  PubMed  CAS  Google Scholar 

  49. Tanemura A, Terando AM, Sim MS et al (2009) CpG island methylator phenotype predicts progression of malignant melanoma. Clin Cancer Res 15:1801–1807

    Article  PubMed  CAS  Google Scholar 

  50. Mori T, Kim J, Yamano T et al (2005) Epigenetic up-regulation of C-C chemokine receptor 7 and C-X-C chemokine receptor 4 expression in melanoma cells. Cancer Res 65:1800–1807

    Article  PubMed  CAS  Google Scholar 

  51. Mori T, Martinez SR, O’Day SJ et al (2006) Estrogen receptor-alpha methylation predicts melanoma progression. Cancer Res 66:6692–6698

    Article  PubMed  CAS  Google Scholar 

  52. Goto Y, Arigami T, Murali R et al (2010) High molecular weight-melanoma-associated antigen as a biomarker of desmoplastic melanoma. Pigment Cell Melanoma Res 23:137–140

    Article  PubMed  CAS  Google Scholar 

  53. Goto Y, Ferrone S, Arigami T et al (2008) Human high molecular weight-melanoma-associated antigen: utility for detection of metastatic melanoma in sentinel lymph nodes. Clin Cancer Res 14:3401–3407

    Article  PubMed  CAS  Google Scholar 

  54. Hoon DS, Spugnardi M, Kuo C et al (2004) Profiling epigenetic inactivation of tumor suppressor genes in tumors and plasma from cutaneous melanoma patients. Oncogene 23:4014–4022

    Article  PubMed  CAS  Google Scholar 

  55. Kitago M, Martinez SR, Nakamura T et al (2009) Regulation of RUNX3 tumor suppressor gene expression in cutaneous melanoma. Clin Cancer Res 15:2988–2994

    Article  PubMed  CAS  Google Scholar 

  56. Nguyen T, Kuo C, Nicholl MB et al (2011) Downregulation of microRNA-29c is associated with hypermethylation of tumor-related genes and disease outcome in cutaneous melanoma. Epigenetics 6:388–394

    Article  PubMed  CAS  Google Scholar 

  57. de Maat MF, van de Velde CJ, van der Werff MP et al (2008) Quantitative analysis of methylation of genomic loci in early-stage rectal cancer predicts distant recurrence. J Clin Oncol 26:2327–2335

    Article  PubMed  CAS  Google Scholar 

  58. Haqq C, Nosrati M, Sudilovsky D et al (2005) The gene expression signatures of melanoma progression. Proc Natl Acad Sci USA 102:6092–6097

    Article  PubMed  CAS  Google Scholar 

  59. Kashani-Sabet M, Rangel J, Torabian S et al (2009) A multi-marker assay to distinguish malignant melanomas from benign nevi. Proc Natl Acad Sci USA 106:6268–6272

    Article  PubMed  CAS  Google Scholar 

  60. Kashani-Sabet M, Venna S, Nosrati M et al (2009) A multimarker prognostic assay for primary cutaneous melanoma. Clin Cancer Res 15:6987–6992

    Article  PubMed  CAS  Google Scholar 

  61. Rangel J, Torabian S, Shaikh L et al (2006) Prognostic significance of nuclear receptor coactivator-3 overexpression in primary cutaneous melanoma. J Clin Oncol 24:4565–4569

    Article  PubMed  CAS  Google Scholar 

  62. Rangel J, Nosrati M, Torabian S et al (2008) Osteopontin as a molecular prognostic marker for melanoma. Cancer 112:144–150

    Article  PubMed  Google Scholar 

  63. Rangel J, Nosrati M, Leong SP et al (2008) Novel role for RGS1 in melanoma progression. Am J Surg Pathol 32:1207–1212

    Article  PubMed  Google Scholar 

  64. Mastrangelo MJ, Bellet RE, Berkelhammer J et al (1975) Regression of pulmonary metastatic disease associated with intralesional BCG therapy of intracutaneous melanoma metastases. Cancer 36:1305–1308

    Article  PubMed  CAS  Google Scholar 

  65. Agarwala SS, Neuberg D, Park Y et al (2004) Mature results of a phase III randomized trial of bacillus Calmette-Guerin (BCG) versus observation and BCG plus dacarbazine versus BCG in the adjuvant therapy of American Joint Committee on Cancer Stage I-III melanoma (E1673): a trial of the Eastern Oncology Group. Cancer 100:1692–1698

    Article  PubMed  CAS  Google Scholar 

  66. Bedikian AY, Richards J, Kharkevitch D et al (2010) A phase 2 study of high-dose Allovectin-7 in patients with advanced metastatic melanoma. Melanoma Res 20:218–226

    PubMed  CAS  Google Scholar 

  67. Senzer NN, Kaufman HL, Amatruda T et al (2009) Phase II clinical trial of a granulocyte-macrophage colony-stimulating factor-encoding, second-generation oncolytic herpesvirus in patients with unresectable metastatic melanoma. J Clin Oncol 27:5763–5771

    Article  PubMed  CAS  Google Scholar 

  68. Thompson JF, Hersey P, Wachter E (2008) Chemoablation of metastatic melanoma using intralesional Rose Bengal. Melanoma Res 18:405–411

    Article  PubMed  Google Scholar 

  69. Gimbel MI, Delman KA, Zager JS (2008) Therapy for unresectable recurrent and in-transit extremity melanoma. Cancer Control 15:225–232

    PubMed  Google Scholar 

  70. Beasley GM, Petersen RP, Yoo J et al (2008) Isolated limb infusion for in-transit malignant melanoma of the extremity: a well-tolerated but less effective alternative to hyperthermic isolated limb perfusion. Ann Surg Oncol 15:2195–2205

    Article  PubMed  Google Scholar 

  71. Lindner P, Doubrovsky A, Kam PC et al (2002) Prognostic factors after isolated limb infusion with cytotoxic agents for melanoma. Ann Surg Oncol 9:127–136

    PubMed  Google Scholar 

  72. Kroon HM, Moncrieff M, Kam PC et al (2008) Outcomes following isolated limb infusion for melanoma. A 14-year experience. Ann Surg Oncol 15:3003–3013

    Article  PubMed  Google Scholar 

  73. Fraker DL (1999) Hyperthermic regional perfusion for melanoma and sarcoma of the limbs. Curr Probl Surg 36:841–907

    PubMed  CAS  Google Scholar 

  74. Beasley GM, Caudle A, Petersen RP et al (2009) A multi-institutional experience of isolated limb infusion: defining response and toxicity in the US. J Am Coll Surg 208:706–715; discussion 715–717

    Google Scholar 

  75. Santillan AA, Delman KA, Beasley GM et al (2009) Predictive factors of regional toxicity and serum creatine phosphokinase levels after isolated limb infusion for melanoma: a multi-institutional analysis. Ann Surg Oncol 16:2570–2578

    Article  PubMed  Google Scholar 

  76. Wieberdink J, Benckhuysen C, Braat RP et al (1982) Dosimetry in isolation perfusion of the limbs by assessment of perfused tissue volume and grading of toxic tissue reactions. Eur J Cancer Clin Oncol 18:905–910

    Article  PubMed  CAS  Google Scholar 

  77. Chai CY, Deneve JL, Beasley GM et al (2012) A multi-institutional experience of repeat regional chemotherapy for recurrent melanoma of extremities. Ann Surg Oncol 19:1637–1643

    Article  PubMed  Google Scholar 

  78. Beasley GM, Riboh JC, Augustine CK et al (2011) Prospective multicenter phase II trial of systemic ADH-1 in combination with melphalan via isolated limb infusion in patients with advanced extremity melanoma. J Clin Oncol 29:1210–1215

    Article  PubMed  CAS  Google Scholar 

  79. Augustine CK, Toshimitsu H, Jung SH et al (2010) Sorafenib, a multikinase inhibitor, enhances the response of melanoma to regional chemotherapy. Mol Cancer Ther 9:2090–2101

    Article  PubMed  CAS  Google Scholar 

  80. Curley SA, Newman RA, Dougherty TB et al (1994) Complete hepatic venous isolation and extracorporeal chemofiltration as treatment for human hepatocellular carcinoma: a phase I study. Ann Surg Oncol 1:389–399

    Article  PubMed  CAS  Google Scholar 

  81. Pingpank JF, Libutti SK, Chang R et al (2005) Phase I study of hepatic arterial melphalan infusion and hepatic venous hemofiltration using percutaneously placed catheters in patients with unresectable hepatic malignancies. J Clin Oncol 23:3465–3474

    Article  PubMed  CAS  Google Scholar 

  82. Alexander HR Jr, Libutti SK, Pingpank JF et al (2003) Hyperthermic isolated hepatic perfusion using melphalan for patients with ocular melanoma metastatic to liver. Clin Cancer Res 9:6343–6349

    PubMed  CAS  Google Scholar 

  83. Pingpank JF, Hughes MS, Alexander HR et al (2010) A phase III random assignment trial comparing percutaneous hepatic perfusion with melphalan (PHP-mel) to standard of care for patients with hepatic metastases from metastatic ocular or cutaneous melanoma. In: Presented at the American Society of Clinical Oncology, June 2010

  84. Pingpank JF, Hughes M, Alexander HR et al (2011) Percutaneous hepatic perfusion (PHP) vs. best alternative care (BAC) for patients with melanoma liver metastases—efficacy update of the phase 3 trial (NCT00324727). In: European Multidisciplinary Cancer Congress. Stockholm, Sweden, Sept 2011

  85. Zager JS, JF. P (2011) Percutaneous hepatic perfusion (PHP) vs. best alternative care (BAC) for patients (pts) with melanoma liver metastases: updated data from the phase III trial. In: International Melanoma Centers Meeting, Tampa, Florida. Pigment Cell Melanoma Res 24:1010–1011

  86. Balch CM, Soong SJ, Gershenwald JE et al (2001) Prognostic factors analysis of 17,600 melanoma patients: validation of the American Joint Committee on Cancer melanoma staging system. J Clin Oncol 19:3622–3634

    PubMed  CAS  Google Scholar 

  87. van Akkooi AC, de Wilt JH, Verhoef C et al (2006) Clinical relevance of melanoma micrometastases (<0.1 mm) in sentinel nodes: are these nodes to be considered negative? Ann Oncol 17:1578–1585

    Article  PubMed  Google Scholar 

  88. van Akkooi AC, Nowecki ZI, Voit C et al (2008) Sentinel node tumor burden according to the Rotterdam criteria is the most important prognostic factor for survival in melanoma patients: a multicenter study in 388 patients with positive sentinel nodes. Ann Surg 248:949–955

    Article  PubMed  Google Scholar 

  89. Leong SP, Steinmetz I, Habib FA et al (1997) Optimal selective sentinel lymph node dissection in primary malignant melanoma. Arch Surg 132:666–672; discussion 673

    Article  PubMed  CAS  Google Scholar 

  90. Leong SP (2004) Sentinel lymph node mapping and selective lymphadenectomy: the standard of care for melanoma. Curr Treat Options Oncol 5:185–194

    Article  PubMed  Google Scholar 

  91. Ranieri JM, Wagner JD, Azuaje R et al (2002) Prognostic importance of lymph node tumor burden in melanoma patients staged by sentinel node biopsy. Ann Surg Oncol 9:975–981

    Article  PubMed  Google Scholar 

  92. Carlson GW, Murray DR, Lyles RH et al (2003) The amount of metastatic melanoma in a sentinel lymph node: does it have prognostic significance? Ann Surg Oncol 10:575–581

    Article  PubMed  Google Scholar 

  93. Reeves ME, Delgado R, Busam KJ et al (2003) Prediction of nonsentinel lymph node status in melanoma. Ann Surg Oncol 10:27–31

    Article  PubMed  Google Scholar 

  94. Lee JH, Essner R, Torisu-Itakura H et al (2004) Factors predictive of tumor-positive nonsentinel lymph nodes after tumor-positive sentinel lymph node dissection for melanoma. J Clin Oncol 22:3677–3684

    Article  PubMed  Google Scholar 

  95. Scolyer RA, Li LX, McCarthy SW et al (2004) Micromorphometric features of positive sentinel lymph nodes predict involvement of nonsentinel nodes in patients with melanoma. Am J Clin Pathol 122:532–539

    Article  PubMed  Google Scholar 

  96. Sabel MS, Griffith K, Sondak VK et al (2005) Predictors of nonsentinel lymph node positivity in patients with a positive sentinel node for melanoma. J Am Coll Surg 201:37–47

    Article  PubMed  Google Scholar 

  97. Debarbieux S, Duru G, Dalle S et al (2007) Sentinel lymph node biopsy in melanoma: a micromorphometric study relating to prognosis and completion lymph node dissection. Br J Dermatol 157:58–67

    Article  PubMed  CAS  Google Scholar 

  98. Scheri RP, Essner R, Turner RR et al (2007) Isolated tumor cells in the sentinel node affect long-term prognosis of patients with melanoma. Ann Surg Oncol 14:2861–2866

    Article  PubMed  Google Scholar 

  99. Page AJ, Carlson GW, Delman KA et al (2007) Prediction of nonsentinel lymph node involvement in patients with a positive sentinel lymph node in malignant melanoma. Am Surg 73:674–678; discussion 678–679

    PubMed  Google Scholar 

  100. Glumac N, Hocevar M, Zadnik V et al (2008) Sentinel lymph node micrometastasis may predict non-sentinel involvement in cutaneous melanoma patients. J Surg Oncol 98:46–48

    Article  PubMed  Google Scholar 

  101. Rossi CR, De Salvo GL, Bonandini E et al (2008) Factors predictive of nonsentinel lymph node involvement and clinical outcome in melanoma patients with metastatic sentinel lymph node. Ann Surg Oncol 15:1202–1210

    Article  PubMed  Google Scholar 

  102. Frankel TL, Griffith KA, Lowe L et al (2008) Do micromorphometric features of metastatic deposits within sentinel nodes predict nonsentinel lymph node involvement in melanoma? Ann Surg Oncol 15:2403–2411

    Article  PubMed  Google Scholar 

  103. Guggenheim M, Dummer R, Jung FJ et al (2008) The influence of sentinel lymph node tumour burden on additional lymph node involvement and disease-free survival in cutaneous melanoma–a retrospective analysis of 392 cases. Br J Cancer 98:1922–1928

    Article  PubMed  CAS  Google Scholar 

  104. Gershenwald JE, Andtbacka RH, Prieto VG et al (2008) Microscopic tumor burden in sentinel lymph nodes predicts synchronous nonsentinel lymph node involvement in patients with melanoma. J Clin Oncol 26:4296–4303

    Article  PubMed  Google Scholar 

  105. van der Ploeg IM, Kroon BB, Antonini N et al (2009) Comparison of three micromorphometric pathology classifications of melanoma metastases in the sentinel node. Ann Surg 250:301–304

    Article  PubMed  Google Scholar 

  106. Francischetto T, Spector N, Neto Rezende JF et al (2010) Influence of sentinel lymph node tumor burden on survival in melanoma. Ann Surg Oncol 17:1152–1158

    Article  PubMed  Google Scholar 

  107. Satzger I, Volker B, Meier A et al (2007) Prognostic significance of isolated HMB45 or Melan A positive cells in melanoma sentinel lymph nodes. Am J Surg Pathol 31:1175–1180

    Article  PubMed  Google Scholar 

  108. White RL Jr, Ayers GD, Stell VH et al (2011) Factors predictive of the status of sentinel lymph nodes in melanoma patients from a large multicenter database. Ann Surg Oncol 18:3593–3600

    Article  PubMed  Google Scholar 

  109. Dewar DJ, Newell B, Green MA et al (2004) The microanatomic location of metastatic melanoma in sentinel lymph nodes predicts nonsentinel lymph node involvement. J Clin Oncol 22:3345–3349

    Article  PubMed  CAS  Google Scholar 

  110. Bachter D, Balda BR, Vogt H et al (1998) Primary therapy of malignant melanomas: sentinel lymphadenectomy. Int J Dermatol 37:278–282

    Article  PubMed  CAS  Google Scholar 

  111. Pijpers R, Borgstein PJ, Meijer S et al (1997) Sentinel node biopsy in melanoma patients: dynamic lymphoscintigraphy followed by intraoperative gamma probe and vital dye guidance. World J Surg 21:788–792; discussion 793

    Article  PubMed  CAS  Google Scholar 

  112. Brady MS, Coit DG (1997) Sentinel lymph node evaluation in melanoma. Arch Dermatol 133:1014–1020

    Article  PubMed  CAS  Google Scholar 

  113. Reintgen D, Cruse CW, Wells K et al (1994) The orderly progression of melanoma nodal metastases. Ann Surg 220:759–767

    Article  PubMed  CAS  Google Scholar 

  114. Glass LF, Fenske NA, Messina JL et al (1995) The role of selective lymphadenectomy in the management of patients with malignant melanoma. Dermatol Surg 21:979–983

    Article  PubMed  CAS  Google Scholar 

  115. Krag DN, Meijer SJ, Weaver DL et al (1995) Minimal-access surgery for staging of malignant melanoma. Arch Surg 130:654–658; discussion 659–660

    Article  PubMed  CAS  Google Scholar 

  116. Thompson JF, McCarthy WH, Bosch CM et al (1995) Sentinel lymph node status as an indicator of the presence of metastatic melanoma in regional lymph nodes. Melanoma Res 5:255–260

    Article  PubMed  CAS  Google Scholar 

  117. Lenisa L, Santinami M, Belli F et al (1999) Sentinel node biopsy and selective lymph node dissection in cutaneous melanoma patients. J Exp Clin Cancer Res 18:69–74

    PubMed  CAS  Google Scholar 

  118. Wagner JD, Gordon MS, Chuang TY et al (2000) Predicting sentinel and residual lymph node basin disease after sentinel lymph node biopsy for melanoma. Cancer 89:453–462

    Article  PubMed  CAS  Google Scholar 

  119. Starz H, Balda BR, Kramer KU et al (2001) A micromorphometry-based concept for routine classification of sentinel lymph node metastases and its clinical relevance for patients with melanoma. Cancer 91:2110–2121

    Article  PubMed  CAS  Google Scholar 

  120. Starz H, Siedlecki K, Balda BR (2004) Sentinel lymphonodectomy and s-classification: a successful strategy for better prediction and improvement of outcome of melanoma. Ann Surg Oncol 11:162S–168S

    PubMed  Google Scholar 

  121. van der Ploeg AP, van Akkooi AC, Rutkowski P et al (2011) Prognosis in patients with sentinel node-positive melanoma is accurately defined by the combined Rotterdam tumor load and Dewar topography criteria. J Clin Oncol 29:2206–2214

    Article  PubMed  Google Scholar 

  122. Leong SP (2004) Paradigm of metastasis for melanoma and breast cancer based on the sentinel lymph node experience. Ann Surg Oncol 11:192S–197S

    PubMed  Google Scholar 

  123. Baehner FL, Li R, Jenkins T et al (2012) The impact of primary melanoma thickness and microscopic tumor burden in sentinel lymph nodes on melanoma patient survival. Ann Surg Oncol 19:1034–1042

    Article  PubMed  Google Scholar 

  124. Hellman S (1994) Karnofsky Memorial Lecture. Natural history of small breast cancers. J Clin Oncol 12:2229–2234

    PubMed  CAS  Google Scholar 

  125. Morton DL, Thompson JF, Cochran AJ et al (2006) Sentinel-node biopsy or nodal observation in melanoma. N Engl J Med 355:1307–1317

    Article  PubMed  CAS  Google Scholar 

  126. Amersi F, Morton DL (2007) The role of sentinel lymph node biopsy in the management of melanoma. Adv Surg 41:241–256

    Article  PubMed  Google Scholar 

  127. Eggermont AM, Suciu S, Testori A et al (2012) Ulceration and stage are predictive of interferon efficacy in melanoma: results of the phase III adjuvant trials EORTC 18952 and EORTC 18991. Eur J Cancer 48:218–225

    Article  PubMed  CAS  Google Scholar 

  128. Eigentler TK, Caroli UM, Radny P et al (2003) Palliative therapy of disseminated malignant melanoma: a systematic review of 41 randomised clinical trials. Lancet Oncol 4:748–759

    Article  PubMed  CAS  Google Scholar 

  129. Curtin JA, Fridlyand J, Kageshita T et al (2005) Distinct sets of genetic alterations in melanoma. N Engl J Med 353:2135–2147

    Article  PubMed  CAS  Google Scholar 

  130. Flaherty KT, Puzanov I, Kim KB et al (2010) Inhibition of mutated, activated BRAF in metastatic melanoma. N Engl J Med 363:809–819

    Article  PubMed  CAS  Google Scholar 

  131. Sosman JA, Kim KB, Schuchter L et al (2012) Survival in BRAF V600-mutant advanced melanoma treated with vemurafenib. N Engl J Med 366:707–714

    Article  PubMed  CAS  Google Scholar 

  132. Greger JG, Eastman SD, Zhang V et al (2012) Combinations of BRAF, MEK, and PI3K/mTOR inhibitors overcome acquired resistance to the BRAF inhibitor GSK2118436 dabrafenib, mediated by NRAS or MEK mutations. Mol Cancer Ther 11:909–920

    Article  PubMed  CAS  Google Scholar 

  133. Guo J, Si L, Kong Y et al (2011) Phase II, open-label, single-arm trial of imatinib mesylate in patients with metastatic melanoma harboring c-Kit mutation or amplification. J Clin Oncol 29:2904–2909

    Article  PubMed  CAS  Google Scholar 

  134. Kim KB, Sosman JA, Fruehauf JP et al (2012) BEAM: a randomized phase II study evaluating the activity of bevacizumab in combination with carboplatin plus paclitaxel in patients with previously untreated advanced melanoma. J Clin Oncol 30:34–41

    Article  PubMed  CAS  Google Scholar 

  135. Eggermont AM, Robert C (2011) New drugs in melanoma: it’s a whole new world. Eur J Cancer 47:2150–2157

    Article  PubMed  Google Scholar 

  136. Morton DL, Eilber FR, Holmes EC et al (1974) BCG immunotherapy of malignant melanoma: summary of a seven-year experience. Ann Surg 180:635–643

    Article  PubMed  CAS  Google Scholar 

  137. Fourcade J, Sun Z, Benallaoua M et al (2010) Upregulation of Tim-3 and PD-1 expression is associated with tumor antigen-specific CD8+ T cell dysfunction in melanoma patients. J Exp Med 207:2175–2186

    Article  PubMed  CAS  Google Scholar 

  138. Leong SP, Zuber M, Ferris RL et al (2011) Impact of nodal status and tumor burden in sentinel lymph nodes on the clinical outcomes of cancer patients. J Surg Oncol 103:518–530

    Article  PubMed  Google Scholar 

  139. Tawbi HA, Buch SC (2010) Chemotherapy resistance abrogation in metastatic melanoma. Clin Adv Hematol Oncol 8:259–266

    PubMed  Google Scholar 

  140. Tarhini AA, Stuckert J, Lee S et al (2009) Prognostic significance of serum S100B protein in high-risk surgically resected melanoma patients participating in Intergroup Trial ECOG 1694. J Clin Oncol 27:38–44

    Article  PubMed  Google Scholar 

  141. Gogas H, Kirkwood JM, Falk CS et al (2010) Correlation of molecular human leukocyte antigen typing and outcome in high-risk melanoma patients receiving adjuvant interferon. Cancer 116:4326–4333

    Article  PubMed  Google Scholar 

  142. Gogas H, Ioannovich J, Dafni U et al (2006) Prognostic significance of autoimmunity during treatment of melanoma with interferon. N Engl J Med 354:709–718

    Article  PubMed  CAS  Google Scholar 

  143. Hodi FS, O’Day SJ, McDermott DF et al (2010) Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 363:711–723

    Article  PubMed  CAS  Google Scholar 

  144. Salama AK, Hodi FS (2011) Cytotoxic T-lymphocyte-associated antigen-4. Clin Cancer Res 17:4622–4628

    Article  PubMed  CAS  Google Scholar 

  145. Atkins MB, Mier JW, Parkinson DR et al (1988) Hypothyroidism after treatment with interleukin-2 and lymphokine-activated killer cells. N Engl J Med 318:1557–1563

    Article  PubMed  CAS  Google Scholar 

  146. Yurkovetsky ZR, Kirkwood JM, Edington HD et al (2007) Multiplex analysis of serum cytokines in melanoma patients treated with interferon-alpha2b. Clin Cancer Res 13:2422–2428

    Article  PubMed  CAS  Google Scholar 

  147. Moschos SJ, Edington HD, Land SR et al (2006) Neoadjuvant treatment of regional stage IIIB melanoma with high-dose interferon alfa-2b induces objective tumor regression in association with modulation of tumor infiltrating host cellular immune responses. J Clin Oncol 24:3164–3171

    Article  PubMed  CAS  Google Scholar 

  148. Wang W, Edington HD, Rao UN et al (2007) Modulation of signal transducers and activators of transcription 1 and 3 signaling in melanoma by high-dose IFNalpha2b. Clin Cancer Res 13:1523–1531

    Article  PubMed  CAS  Google Scholar 

  149. Falchook GS, Long GV, Kurzrock R et al (2012) Dabrafenib in patients with melanoma, untreated brain metastases, and other solid tumours: a phase 1 dose-escalation trial. Lancet 379:1893–1901

    Article  PubMed  CAS  Google Scholar 

  150. Tarhini AA, Edington H, Butterfield LH et al (2012) Neoadjuvant ipilimumab in locally/regionally advanced melanoma: clinical outcome and immune monitoring. Proceedings. J Clin Oncol 30:Abstr 8533

  151. Tarhini AA, Cherian J, Moschos SJ et al (2012) Safety and efficacy of combination immunotherapy with interferon alfa-2b and tremelimumab in patients with stage IV melanoma. J Clin Oncol 30:322–328

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments by John Kirkwood

The project described was supported by Award Number P50CA121973 from the National Cancer Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Stanley P. L. Leong.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Leong, S.P.L., Mihm, M.C., Murphy, G.F. et al. Progression of cutaneous melanoma: implications for treatment. Clin Exp Metastasis 29, 775–796 (2012). https://doi.org/10.1007/s10585-012-9521-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10585-012-9521-1

Keywords

Navigation