Clinical & Experimental Metastasis

, Volume 28, Issue 4, pp 327–336 | Cite as

Genetic factors in metastatic progression of cutaneous melanoma: the future role of circulating melanoma cells in prognosis and management

  • A. Ireland
  • M. Millward
  • R. Pearce
  • M. Lee
  • M. Ziman


The greatest potential for improvement of outcome for patients with Cutaneous Malignant Melanoma lies in the prevention of systemic metastasis. Despite extensive investigation, current prognostic indicators either alone or in combination, although related to melanoma progression, are not sufficient to accurately predict the pattern of progression and outcome for any individual patient. Metastasis related death has been recorded in patients initially diagnosed with early stage tumour as well as in patients many years after initial tumour removal. The trouble finding a predictable pattern in the puzzle of melanoma progression may be linked to the fact that most of the material studied for prognosis is either, cutaneous primaries or metastatic deposits, rather than the melanoma cells in the circulatory system which are responsible for disease progression. In this review article we discuss the potential use of circulating tumour cell (CTC) detection and quantification for identifying patients at risk of metastatic deposits. We also discuss current therapies for the treatment of metastatic melanoma and analyse how CTCs may be used to evaluate the effectiveness of current therapies and to pinpoint patients who require further treatment.


Melanoma Metastasis Circulating cells Markers of disease progression Patient monitoring 



We would like to thank Peter Mathews for helpful discussions and acknowledge funding from The Cancer Council of Western Australia, the National Health and Medical Research Council of Australia and the Cancer and Palliative Care Research and Evaluation Unit.


  1. 1.
    Lewis TB et al (2005) Molecular classification of melanoma using real-time quantitative reverse transcriptase-polymerase chain reaction. Cancer 104:1678–1686PubMedGoogle Scholar
  2. 2.
    Australasian Association of Cancer Registries (2006) Australian Institute of Health and Welfare. Cited 28/4/10
  3. 3.
    Jack A et al (2006) The treatment of melanoma with an emphasis on immunotherapeutic strategies. Surg Oncol 15:13–24PubMedGoogle Scholar
  4. 4.
    Lee RT et al (2008) Melanoma presenting as circulating tumor cells associated with failed angiogenesis. Melanoma Res 18:289–294PubMedGoogle Scholar
  5. 5.
    Zbytek B et al (2008) Current concepts of metastasis in melanoma. Expert Rev Dermatol 3:569–585PubMedGoogle Scholar
  6. 6.
    Yang AS, Chapman PB (2009) The history and future of chemotherapy for melanoma. Hematol Oncol Clin North Am 23:583–597PubMedGoogle Scholar
  7. 7.
    Breslow A (1975) Tumor thickness, level of invasion and node dissection in stage I cutaneous melanoma. Ann Surg 182:572–575PubMedGoogle Scholar
  8. 8.
    Balch CM et al (2001) Final version of the American Joint Committee on Cancer staging system for cutaneous melanoma. J Clin Oncol 19:3635–3648PubMedGoogle Scholar
  9. 9.
    Eton O et al (1998) Prognostic factors for survival of patients treated systemically for disseminated melanoma. J Clin Oncol 16:1103–1111PubMedGoogle Scholar
  10. 10.
    Francken AB et al (2008) Prognosis and determinants of outcome following locoregional or distant recurrence in patients with cutaneous melanoma. Ann Surg Oncol 15:1476–1484PubMedGoogle Scholar
  11. 11.
    Thompson JF, Scolyer RA, Kefford RF (2009) Cutaneous melanoma in the era of molecular profiling. Lancet 374:362–365PubMedGoogle Scholar
  12. 12.
    Singh AD et al (2004) The Zimmerman-McLean-Foster hypothesis: 25 years later. Br J Ophthalmol 88:962–967PubMedGoogle Scholar
  13. 13.
    White RM, Zon LI (2008) Melanocytes in development, regeneration, and cancer. Cell Stem Cell 3:242–252PubMedGoogle Scholar
  14. 14.
    Roberts DL et al (2002) U.K. guidelines for the management of cutaneous melanoma. Br J Dermatol 146:7–17PubMedGoogle Scholar
  15. 15.
    Michaelson JS et al (2005) Spread of human cancer cells occurs with probabilities indicative of a nongenetic mechanism. Br J Cancer 93:1244–1249PubMedGoogle Scholar
  16. 16.
    Wascher RA et al (2003) Molecular tumor markers in the blood: early prediction of disease outcome in melanoma patients treated with a melanoma vaccine. J Clin Oncol 21:2558–2563PubMedGoogle Scholar
  17. 17.
    Hoek KS et al (2006) Metastatic potential of melanomas defined by specific gene expression profiles with no BRAF signature. Pigment Cell Res 19:290–302PubMedGoogle Scholar
  18. 18.
    Bockhorn M, Jain RK, Munn LL (2007) Active versus passive mechanisms in metastasis: do cancer cells crawl into vessels, or are they pushed? Lancet Oncol 8:444–448PubMedGoogle Scholar
  19. 19.
    Chen LL et al (2009) Cancer metastasis networks and the prediction of progression patterns. Br J Cancer 101:749–758PubMedGoogle Scholar
  20. 20.
    Butler TP, Gullino PM (1975) Quantitation of cell shedding into efferent blood of mammary adenocarcinoma. Cancer Res 35:512–516PubMedGoogle Scholar
  21. 21.
    Fidler IJ et al (2002) The seed and soil hypothesis: vascularisation and brain metastases. Lancet Oncol 3:53–57PubMedGoogle Scholar
  22. 22.
    Chiang AC, Massague J (2008) Molecular basis of metastasis. N Engl J Med 359:2814–2823PubMedGoogle Scholar
  23. 23.
    Ulmer A et al (2008) Visualization of circulating melanoma cells in peripheral blood of patients with primary uveal melanoma. Clin Cancer Res 14:4469–4474PubMedGoogle Scholar
  24. 24.
    Ulmer A et al (2004) Immunomagnetic enrichment, genomic characterization, and prognostic impact of circulating melanoma cells. Clin Cancer Res 10:531–537PubMedGoogle Scholar
  25. 25.
    Husemann Y et al (2008) Systemic spread is an early step in breast cancer. Cancer Cell 13:58–68PubMedGoogle Scholar
  26. 26.
    Mocellin S et al (2006) The prognostic value of circulating tumor cells in patients with melanoma: a systematic review and meta-analysis. Clin Cancer Res 12:4605–4613PubMedGoogle Scholar
  27. 27.
    Sekine I et al (2002) Relationship between objective responses in phase I trials and potential efficacy of non-specific cytotoxic investigational new drugs. Ann Oncol 13:1300–1306PubMedGoogle Scholar
  28. 28.
    Bhatia S, Tykodi SS, Thompson JA (2009) Treatment of metastatic melanoma: an overview. Oncol 23:488–496Google Scholar
  29. 29.
    T FR Crosby, Coles B, Mason M (2000) Systemic treatments for metastatic cutaneous melanoma. Cochrane Database Syst Rev 2:CD001215Google Scholar
  30. 30.
    Richards JM BA, Gonzalez R, et al. (2005) High-dose Allovectin-7® in patients with advanced metastatic melanoma: final Phase 2 data and design of Phase 3 registration trial. J Clin Oncol 23:16s:7543Google Scholar
  31. 31.
    Shepherd C, Puzanov I, Sosman JA (2010) B-RAF inhibitors: an evolving role in the therapy of malignant melanoma. Curr Oncol Rep 12:146–152PubMedGoogle Scholar
  32. 32.
    Fisher DE et al (2010) Melanoma from bench to bedside: meeting report from the 6th international melanoma congress. Pigment Cell Melanoma Res 23:14–26PubMedGoogle Scholar
  33. 33.
    Modjtahedi H, Essapen S (2009) Epidermal growth factor receptor inhibitors in cancer treatment: advances, challenges and opportunities. Anticancer Drugs 20:851–865PubMedGoogle Scholar
  34. 34.
    Flaherty KT et al (2010) Inhibition of Mutated, Activated BRAF in Metastatic Melanoma. N Engl J Med 363:809–819PubMedGoogle Scholar
  35. 35.
    Mazzocca A, Carloni V (2009) The metastatic process: methodological advances and pharmacological challenges. Curr Med Chem 16:1704–1717PubMedGoogle Scholar
  36. 36.
    Van Den Bossche K, Naeyaert JM, Lambert J (2006) The quest for the mechanism of melanin transfer. Traffic 7:769–778Google Scholar
  37. 37.
    Moustakas A, Heldin CH (2007) Signaling networks guiding epithelial-mesenchymal transitions during embryogenesis and cancer progression. Cancer Sci 98:1512–1520PubMedGoogle Scholar
  38. 38.
    Paterlini-Brechot P, Benali NL (2007) Circulating tumor cells (CTC) detection: clinical impact and future directions. Cancer Lett 253:180–204PubMedGoogle Scholar
  39. 39.
    Pouyssegur J, Dayan F, Mazure NM (2006) Hypoxia signalling in cancer and approaches to enforce tumour regression. Nature 441:437–443PubMedGoogle Scholar
  40. 40.
    Kageshita T et al (2001) Loss of beta-catenin expression associated with disease progression in malignant melanoma. Br J Dermatol 145:210–216PubMedGoogle Scholar
  41. 41.
    Vogelmann R et al (2005) TGFbeta-induced downregulation of E-cadherin-based cell-cell adhesion depends on PI3-kinase and PTEN. J Cell Sci 118:4901–4912PubMedGoogle Scholar
  42. 42.
    Peinado H, Portillo F, Cano A (2004) Transcriptional regulation of cadherins during development and carcinogenesis. Int J Dev Biol 48:365–375PubMedGoogle Scholar
  43. 43.
    Hsu MY et al (2000) E-cadherin expression in melanoma cells restores keratinocyte-mediated growth control and down-regulates expression of invasion-related adhesion receptors. Am J Pathol 156:1515–1525PubMedGoogle Scholar
  44. 44.
    Sanz-Moreno V et al (2008) Rac activation and inactivation control plasticity of tumor cell movement. Cell 135:510–523PubMedGoogle Scholar
  45. 45.
    Egeblad M, Werb Z (2002) New functions for the matrix metalloproteinases in cancer progression. Nat Rev Cancer 2:161–174PubMedGoogle Scholar
  46. 46.
    Lewis CE, Pollard JW (2006) Distinct role of macrophages in different tumor microenvironments. Cancer Res 66:605–612PubMedGoogle Scholar
  47. 47.
    Liotta LA, Kleinerman J, Saidel GM (1974) Quantitative relationships of intravascular tumor cells, tumor vessels, and pulmonary metastases following tumor implantation. Cancer Res 34:997–1004PubMedGoogle Scholar
  48. 48.
    Glinsky GV (1997) Apoptosis in metastatic cancer cells. Crit Rev Oncol Hematol 25:175–186PubMedGoogle Scholar
  49. 49.
    Swartz MA et al (1999) Cells shed from tumours show reduced clonogenicity, resistance to apoptosis, and in vivo tumorigenicity. Br J Cancer 81:756–759PubMedGoogle Scholar
  50. 50.
    Larson CJ et al (2004) Apoptosis of circulating tumor cells in prostate cancer patients. Cytometry A 62:46–53PubMedGoogle Scholar
  51. 51.
    Mehes G et al (2001) Circulating breast cancer cells are frequently apoptotic. Am J Pathol 159:17–20PubMedGoogle Scholar
  52. 52.
    Holmgren L, O’Reilly MS, Folkman J (1995) Dormancy of micrometastases: balanced proliferation and apoptosis in the presence of angiogenesis suppression. Nat Med 1:149–153PubMedGoogle Scholar
  53. 53.
    Nguyen DX, Bos PD, Massague J (2009) Metastasis: from dissemination to organ-specific colonization. Nat Rev Cancer 9:274–284PubMedGoogle Scholar
  54. 54.
    Borsig L et al (2002) Synergistic effects of L- and P-selectin in facilitating tumor metastasis can involve non-mucin ligands and implicate leukocytes as enhancers of metastasis. Proc Natl Acad Sci USA 99:2193–2198PubMedGoogle Scholar
  55. 55.
    Laubli H et al (2006) L-selectin facilitation of metastasis involves temporal induction of Fut7-dependent ligands at sites of tumor cell arrest. Cancer Res 66:1536–1542PubMedGoogle Scholar
  56. 56.
    Fuertes MB et al (2008) Intracellular retention of the NKG2D ligand MHC class I chain-related gene A in human melanomas confers immune privilege and prevents NK cell-mediated cytotoxicity. J Immunol 180:4606–4614PubMedGoogle Scholar
  57. 57.
    Lacreusette A et al (2007) Loss of oncostatin M receptor beta in metastatic melanoma cells. Oncogene 26:881–892PubMedGoogle Scholar
  58. 58.
    Horak CE et al (2008) The role of metastasis suppressor genes in metastatic dormancy. APMIS 116:586–601PubMedGoogle Scholar
  59. 59.
    Eyles J et al (2010) Tumor cells disseminate early, but immunosurveillance limits metastatic outgrowth, in a mouse model of melanoma. J Clin Invest 120:2030–2039PubMedGoogle Scholar
  60. 60.
    Yoshida BA et al (2000) Metastasis-suppressor genes: a review and perspective on an emerging field. J Natl Cancer Inst 92:1717–1730PubMedGoogle Scholar
  61. 61.
    Röcken M (2010) Early tumor dissemination, but late metastasis: insights into tumor dormancy. J Clin Invest 120:1800–1803PubMedGoogle Scholar
  62. 62.
    Harms JF, Welch DR, Miele ME (2003) KISS1 metastasis suppression and emergent pathways. Clin Exp Metastasis 20:11–18PubMedGoogle Scholar
  63. 63.
    Boissan M, Poupon MF, Lacombe ML (2007) NM23 and metastasis suppressor genes: update. Med Sci (Paris) 23:1115–1123Google Scholar
  64. 64.
    Steeg PS, Horak CE, Miller KD (2008) Clinical-translational approaches to the Nm23–H1 metastasis suppressor. Clin Cancer Res 14:5006–5012PubMedGoogle Scholar
  65. 65.
    Gobeil S et al (2008) A genome-wide shRNA screen identifies GAS1 as a novel melanoma metastasis suppressor gene. Genes Dev 22:2932–2940PubMedGoogle Scholar
  66. 66.
    Shevde LA et al (2002) Suppression of human melanoma metastasis by the metastasis suppressor gene, BRMS1. Exp Cell Res 273:229–239PubMedGoogle Scholar
  67. 67.
    Lee CC et al (2008) Improved survival after lymphadenectomy for nodal metastasis from an unknown primary melanoma. J Clin Oncol 26:535–541PubMedGoogle Scholar
  68. 68.
    Vijuk G, Coates AS (1998) Survival of patients with visceral metastatic melanoma from an occult primary lesion: a retrospective matched cohort study. Ann Oncol 9:419–422PubMedGoogle Scholar
  69. 69.
    Zalaudek I et al (2003) Local recurrence in melanoma in situ: influence of sex, age, site of involvement and therapeutic modalities. Br J Dermatol 148:703–708PubMedGoogle Scholar
  70. 70.
    Koyanagi K et al (2005) Serial monitoring of circulating melanoma cells during neoadjuvant biochemotherapy for stage III melanoma: outcome prediction in a multicenter trial. J Clin Oncol 23:8057–8064PubMedGoogle Scholar
  71. 71.
    Kujala E, Mäkitie T, Kivelä T (2003) Very long-term prognosis of patients with malignant uveal melanoma. Investig Ophthalmol Vis Sci 44:4651–4659Google Scholar
  72. 72.
    Wargo JA, Tanabe K (2009) Surgical management of melanoma. Hematol Oncol Clin North Am 23:565–581PubMedGoogle Scholar
  73. 73.
    Ramaswamy S et al (2003) A molecular signature of metastasis in primary solid tumors. Nat Genet 33:49–54PubMedGoogle Scholar
  74. 74.
    Bernards R, Weinberg RA (2002) A progression puzzle. Nature 418:823PubMedGoogle Scholar
  75. 75.
    Waghorne C et al (1988) Genetic evidence for progressive selection and overgrowth of primary tumors by metastatic cell subpopulations. Cancer Res 48:6109–6114PubMedGoogle Scholar
  76. 76.
    Fang D et al (2005) A tumorigenic subpopulation with stem cell properties in melanomas. Cancer Res 65:9328–9337PubMedGoogle Scholar
  77. 77.
    Grichnik JM et al (2006) Melanoma, a tumor based on a mutant stem cell? J Invest Dermatol 126:142–153PubMedGoogle Scholar
  78. 78.
    Monzani E et al (2007) Melanoma contains CD133 and ABCG2 positive cells with enhanced tumourigenic potential. Eur J Cancer 43:935–946PubMedGoogle Scholar
  79. 79.
    Schatton T et al (2008) Identification of cells initiating human melanomas. Nature 451:345–349PubMedGoogle Scholar
  80. 80.
    Zabierowski SE, Herlyn M (2008) Melanoma stem cells: the dark seed of melanoma. J Clin Oncol 26:2890–2894PubMedGoogle Scholar
  81. 81.
    Wicha MS (2006) Cancer stem cells and metastasis: lethal seeds. Clin Cancer Res 12:5606–5607PubMedGoogle Scholar
  82. 82.
    Pantel K, Alix-Panabieres C, Riethdorf S (2009) Cancer micrometastases. Nat Rev Clin Oncol 6:339–351PubMedGoogle Scholar
  83. 83.
    Keshet GI et al (2008) MDR1 expression identifies human melanoma stem cells. Biochem Biophys Res Commun 368:930–936PubMedGoogle Scholar
  84. 84.
    Schatton T, Frank MH (2008) Cancer stem cells and human malignant melanoma. Pigment Cell Melanoma Res 21:39–55PubMedGoogle Scholar
  85. 85.
    Smalley KS, Herlyn M (2009) Integrating tumor-initiating cells into the paradigm for melanoma targeted therapy. Int J Cancer 124:1245–1250PubMedGoogle Scholar
  86. 86.
    Hess AR, Seftor EA, Gruman LM, Kinch MS, Seftor RE, Hendrix MJ (2006) VE-cadherin regulates EphA2 in aggressive melanoma cells through a novel signaling pathway: implications for vasculogenic mimicry. Cancer Biol Ther 5:228–233PubMedGoogle Scholar
  87. 87.
    La Porta C (2009) Cancer stem cells: lessons from melanoma. Stem Cell Rev 5:61–65PubMedGoogle Scholar
  88. 88.
    Roesch A et al (2010) A temporarily distinct subpopulation of slow-cycling melanoma cells is required for continuous tumor growth. Cell 141:583–594PubMedGoogle Scholar
  89. 89.
    Hoek KS, Goding CR (2010) Cancer stem cells versus phenotype-switching in melanoma. Pigment Cell Melanoma Res 23:746–759PubMedGoogle Scholar
  90. 90.
    Bennett DC (2008) How to make a melanoma: what do we know of the primary clonal events? Pigment Cell Melanoma Res 21:27–38PubMedGoogle Scholar
  91. 91.
    Bosserhoff AK (2006) Novel biomarkers in malignant melanoma. Clin Chim Acta 367:28–35PubMedGoogle Scholar
  92. 92.
    Gogas H et al (2009) Biomarkers in melanoma. Ann Oncol 20(Suppl 6):vi8–vi13PubMedGoogle Scholar
  93. 93.
    Medic S et al (2007) Molecular markers of circulating melanoma cells. Pigment Cell Res 20:80–91PubMedGoogle Scholar
  94. 94.
    Koyanagi K et al (2006) Association of circulating tumor cells with serum tumor-related methylated DNA in peripheral blood of melanoma patients. Cancer Res 66:6111–6117PubMedGoogle Scholar
  95. 95.
    Xi L et al (2007) Optimal markers for real-time quantitative reverse transcription PCR detection of circulating tumor cells from melanoma, breast, colon, esophageal, head and neck, and lung cancers. Clin Chem 53:1206–1215PubMedGoogle Scholar
  96. 96.
    Koyanagi K et al (2006) Microphthalmia transcription factor as a molecular marker for circulating tumor cell detection in blood of melanoma patients. Clin Cancer Res 12:1137–1143PubMedGoogle Scholar
  97. 97.
    Alonso SR et al (2007) A high-throughput study in melanoma identifies epithelial-mesenchymal transition as a major determinant of metastasis. Cancer Res 67:3450–3460PubMedGoogle Scholar
  98. 98.
    Mandruzzato S et al (2006) A gene expression signature associated with survival in metastatic melanoma. J Transl Med 4:50PubMedGoogle Scholar
  99. 99.
    Talantov D et al (2005) Novel genes associated with malignant melanoma but not benign melanocytic lesions. Clin Cancer Res 11:7234–7242PubMedGoogle Scholar
  100. 100.
    Tucci MG et al (2007) Involvement of E-cadherin, beta-catenin, Cdc42 and CXCR4 in the progression and prognosis of cutaneous melanoma. Br J Dermatol 157:1212–1216PubMedGoogle Scholar
  101. 101.
    Kauffmann A et al (2008) High expression of DNA repair pathways is associated with metastasis in melanoma patients. Oncogene 27:565–573PubMedGoogle Scholar
  102. 102.
    Winnepenninckx V et al (2006) Gene expression profiling of primary cutaneous melanoma and clinical outcome. J Natl Cancer Inst 98:472–482PubMedGoogle Scholar
  103. 103.
    Eberle J et al (2008) Apoptosis pathways and oncolytic adenoviral vectors: promising targets and tools to overcome therapy resistance of malignant melanoma. Exp Dermatol 17:1–11PubMedGoogle Scholar
  104. 104.
    Medic S, Ziman M (2009) PAX3 across the spectrum: from melanoblast to melanoma. Crit Rev Biochem Mol Biol 44:85–97PubMedGoogle Scholar
  105. 105.
    Adams JM, Strasser A (2008) Is tumor growth sustained by rare cancer stem cells or dominant clones? Cancer Res 68:4018–4021PubMedGoogle Scholar
  106. 106.
    Carreira S et al (2006) Mitf regulation of Dia1 controls melanoma proliferation and invasiveness. Genes Dev 20:3426–3439PubMedGoogle Scholar
  107. 107.
    Gupta PB et al (2005) The evolving portrait of cancer metastasis. Cold Spring Harb Symp Quant Biol 70:291–297PubMedGoogle Scholar
  108. 108.
    McArdle L et al (2005) Microarray analysis of phosphatase gene expression in human melanoma. Br J Dermatol 152:925–930PubMedGoogle Scholar
  109. 109.
    Topczewska JM et al (2006) Embryonic and tumorigenic pathways converge via Nodal signaling: role in melanoma aggressiveness. Nat Med 12:925–932PubMedGoogle Scholar
  110. 110.
    Kubic JD et al (2008) Pigmentation PAX-ways: the role of Pax3 in melanogenesis, melanocyte stem cell maintenance, and disease. Pigment Cell Melanoma Res 21:627–645PubMedGoogle Scholar
  111. 111.
    Lang D et al (2005) Pax3 functions at a nodal point in melanocyte stem cell differentiation. Nature 433:884–887PubMedGoogle Scholar
  112. 112.
    Plummer RS et al (2008) PAX3 expression in primary melanomas and nevi. Mod Pathol 21:525–530PubMedGoogle Scholar
  113. 113.
    Meng S et al (2004) Circulating tumor cells in patients with breast cancer dormancy. Clin Cancer Res 10:8152–8162PubMedGoogle Scholar
  114. 114.
    Cools-Lartigue JJ et al (2008) Immunomagnetic isolation and in vitro expansion of human uveal melanoma cell lines. Mol Vis 14:50–55PubMedGoogle Scholar
  115. 115.
    Quintana E et al (2008) Efficient tumour formation by single human melanoma cells. Nature 456:593–598PubMedGoogle Scholar
  116. 116.
    Lewis KD et al (2008) A phase II study of the heparanase inhibitor PI-88 in patients with advanced melanoma. Invest New Drugs 26:89–94PubMedGoogle Scholar
  117. 117.
    Tewes M et al (2009) Molecular profiling and predictive value of circulating tumor cells in patients with metastatic breast cancer: an option for monitoring response to breast cancer related therapies. Breast Cancer Res Treat 115:581–590PubMedGoogle Scholar
  118. 118.
    Fehm T et al (2008) Micrometastatic spread in breast cancer: detection, molecular characterization and clinical relevance. Breast Cancer Res 10(Suppl 1):S1PubMedGoogle Scholar
  119. 119.
    Cristofanilli M et al (2004) Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Engl J Med 351:781–791PubMedGoogle Scholar
  120. 120.
    Dawood S, Cristofanilli M (2007) Integrating circulating tumor cell assays into the management of breast cancer. Curr Treatment Options Oncol 8:89–95Google Scholar

Copyright information

© Springer Science+Business Media B.V. 2011

Authors and Affiliations

  • A. Ireland
    • 1
  • M. Millward
    • 1
  • R. Pearce
    • 2
  • M. Lee
    • 4
  • M. Ziman
    • 2
    • 3
  1. 1.Department of MedicineUniversity of Western AustraliaCrawleyAustralia
  2. 2. ECU Melanoma Research Foundation, School of Exercise, Biomedical and Health Science, Edith Cowan UniversityPerthAustralia
  3. 3.Department of Pathology and Laboratory MedicineUniversity of Western AustraliaCrawleyAustralia
  4. 4.School of Surgery, University of Western AustraliaCrawleyAustralia

Personalised recommendations