Biomarkers in melanoma

Biomarkers are tumour- or host-related factors that correlate with tumour biological behaviour and patient prognosis. High-throughput analytical techniques—DNA and RNA microarrays—have identified numerous possible biomarkers, but their relevance to melanoma progression, clinical outcome and the selection of optimal treatment strategies still needs to be established. The review discusses a possible molecular basis for predictive tissue biomarkers such as melanoma thickness, ulceration and mitotic activity, and provides a list of promising new biomarkers identified from tissue microarrays that needs confirmation by independent, prospectively collected clinical data sets. In addition, common predictive serum biomarkers—lactate dehydrogenase, S100B and melanoma-inhibiting activity—as well as selected investigational serum biomarkers such as TA90IC and YKL-40 are also reviewed. A more accurate, therapeutically predictive classification of human melanomas and selection of patient populations that would profit from therapeutic interventions are among the major challenges expected to be addressed in the future.

[1]  R. Braun,et al.  Updated Swiss guidelines for the treatment and follow-up of cutaneous melanoma. , 2011, Swiss medical weekly.

[2]  W. Shen,et al.  Increased serum levels of S100B are related to the severity of cardiac dysfunction, renal insufficiency and major cardiac events in patients with chronic heart failure. , 2011, Clinical biochemistry.

[3]  G. Calin,et al.  MicroRNAs in body fluids—the mix of hormones and biomarkers , 2011, Nature Reviews Clinical Oncology.

[4]  H. Gogas,et al.  Methods of detection of circulating melanoma cells: a comparative overview. , 2011, Cancer treatment reviews.

[5]  Klaus Pantel,et al.  Cell-free nucleic acids as biomarkers in cancer patients , 2011, Nature Reviews Cancer.

[6]  M. Duffy,et al.  Use of molecular markers for predicting therapy response in cancer patients. , 2011, Cancer treatment reviews.

[7]  Y. Inoue,et al.  The circulating microRNA-221 level in patients with malignant melanoma as a new tumor marker. , 2011, Journal of dermatological science.

[8]  James S Goydos,et al.  Molecular analysis of melanoma-induced sentinel lymph node immune dysfunction , 2011, Cancer Immunology, Immunotherapy.

[9]  G. Poste Bring on the biomarkers , 2011, Nature.

[10]  K. Vickers,et al.  MicroRNAs are Transported in Plasma and Delivered to Recipient Cells by High-Density Lipoproteins , 2011, Nature Cell Biology.

[11]  J. Kirkwood,et al.  Prognostic significance of autoimmunity during treatment of melanoma with interferon , 2006, Seminars in Immunopathology.

[12]  D. Rimm,et al.  Biomarkers: the useful and the not so useful--an assessment of molecular prognostic markers for cutaneous melanoma. , 2010, The Journal of investigative dermatology.

[13]  J. Sosman,et al.  Aberrant DNA methylation in malignant melanoma , 2010, Melanoma research.

[14]  B. Pérez-Gómez,et al.  The immunohistochemical profile of Spitz nevi and conventional (non-Spitzoid) melanomas: a baseline study , 2010, Modern Pathology.

[15]  M. Kashani-Sabet,et al.  Discordance in the histopathologic diagnosis of melanoma at a melanoma referral center. , 2010, Journal of the American Academy of Dermatology.

[16]  N. Polissar,et al.  Immunohistochemical evaluation of p16INK4A, E-cadherin, and cyclin D1 expression in melanoma and Spitz tumors. , 2010, American journal of clinical pathology.

[17]  A. Enk,et al.  Classifying ambiguous melanocytic lesions with FISH and correlation with clinical long-term follow up , 2010, Modern Pathology.

[18]  F. Hodi,et al.  Tumor and Stem Cell Biology Cancer Research Modulation of T-Cell Activation by Malignant Melanoma Initiating Cells , 2010 .

[19]  Jeffrey E Gershenwald,et al.  Final version of 2009 AJCC melanoma staging and classification. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[20]  P. Queirolo,et al.  Melanoma-associated fibroblasts modulate NK cell phenotype and antitumor cytotoxicity , 2009, Proceedings of the National Academy of Sciences.

[21]  A. Hauschild,et al.  A Multimarker Prognostic Assay for Primary Cutaneous Melanoma , 2009, Clinical Cancer Research.

[22]  D. Schadendorf,et al.  Differential Clinical Significance of Individual NKG2D Ligands in Melanoma: Soluble ULBP2 as an Indicator of Poor Prognosis Superior to S100B , 2009, Clinical Cancer Research.

[23]  L. Morrison,et al.  Fluorescence In Situ Hybridization (FISH) as an Ancillary Diagnostic Tool in the Diagnosis of Melanoma , 2009, The American journal of surgical pathology.

[24]  I. Weissman,et al.  CD47 Is Upregulated on Circulating Hematopoietic Stem Cells and Leukemia Cells to Avoid Phagocytosis , 2009, Cell.

[25]  D. Schadendorf,et al.  Serum amyloid A as a prognostic marker in melanoma identified by proteomic profiling. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[26]  M. Bracken,et al.  Tissue biomarkers for prognosis in cutaneous melanoma: a systematic review and meta-analysis. , 2009, Journal of the National Cancer Institute.

[27]  D. Morton,et al.  CpG Island Methylator Phenotype Predicts Progression of Malignant Melanoma , 2009, Clinical Cancer Research.

[28]  William R. Bradley,et al.  Melanoma prognostic model using tissue microarrays and genetic algorithms. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[29]  S. Mocellin,et al.  The prognostic value of serum S100B in patients with cutaneous melanoma: A meta‐analysis , 2008, International journal of cancer.

[30]  M. Duffy,et al.  A personalized approach to cancer treatment: how biomarkers can help. , 2008, Clinical chemistry.

[31]  E. Diamandis,et al.  Strategies for discovering novel cancer biomarkers through utilization of emerging technologies , 2008, Nature Clinical Practice Oncology.

[32]  Peter J. Wild,et al.  HER3 Is a Determinant for Poor Prognosis in Melanoma , 2008, Clinical Cancer Research.

[33]  M. Nosrati,et al.  Novel Role for RGS1 in Melanoma Progression , 2008, The American journal of surgical pathology.

[34]  Daniel B. Martin,et al.  Circulating microRNAs as stable blood-based markers for cancer detection , 2008, Proceedings of the National Academy of Sciences.

[35]  A. Hauschild,et al.  Adjuvant therapy with pegylated interferon alfa-2b versus observation alone in resected stage III melanoma: final results of EORTC 18991, a randomised phase III trial , 2008, The Lancet.

[36]  R. Maestro,et al.  Induction of EMT by twist proteins as a collateral effect of tumor-promoting inactivation of premature senescence. , 2008, Cancer cell.

[37]  A. Hauschild,et al.  EORTC Melanoma Group. Adjuvant therapy with pegylated interferon alfa-2b versus observation alone in resected stage III melanoma: final results of EORTC 18991, a randomised phase III trial. , 2008 .

[38]  M. Martinka,et al.  Role of ING4 in human melanoma cell migration, invasion and patient survival. , 2008, Carcinogenesis.

[39]  R. Dummer,et al.  AZD6244 (ARRY-142886) vs temozolomide (TMZ) in patients (pts) with advanced melanoma: An open-label, randomized, multicenter, phase II study. , 2008 .

[40]  A. Hauschild,et al.  Short German guidelines: Malignant melanoma , 2008, Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG.

[41]  J. Lomas,et al.  The genetics of malignant melanoma. , 2008, Frontiers in bioscience : a journal and virtual library.

[42]  A. D. Van den Abbeele,et al.  Major response to imatinib mesylate in KIT-mutated melanoma. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[43]  Mohamed H. Sayegh,et al.  Identification of cells initiating human melanomas , 2008, Nature.

[44]  D. Bennett How to make a melanoma: what do we know of the primary clonal events? , 2007, Pigment cell & melanoma research.

[45]  M. Nosrati,et al.  Osteopontin as a molecular prognostic marker for melanoma , 2008, Cancer.

[46]  M. Quintanilla,et al.  Molecular biology of malignant melanoma. , 2008, Advances in experimental medicine and biology.

[47]  Y. Kluger,et al.  HSP90 as a marker of progression in melanoma. , 2008, Annals of oncology : official journal of the European Society for Medical Oncology.

[48]  A. Hauschild,et al.  Evidence and interdisciplinary consense-based German guidelines: diagnosis and surveillance of melanoma. , 2007, Melanoma research.

[49]  K. Hoek DNA microarray analyses of melanoma gene expression: a decade in the mines. , 2007, Pigment cell research.

[50]  J. J. van den Oord,et al.  Expression profiling of melanoma cell lines: in search of a progression-related molecular signature. , 2007, Future oncology.

[51]  Hardeep Singh,et al.  Errors in cancer diagnosis: current understanding and future directions. , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[52]  J. Campisi,et al.  Cellular senescence: when bad things happen to good cells , 2007, Nature Reviews Molecular Cell Biology.

[53]  M. Martinka,et al.  Prognostic Significance of Nuclear ING3 Expression in Human Cutaneous Melanoma , 2007, Clinical Cancer Research.

[54]  J. Kirkwood,et al.  Interferon alfa-induced autoimmunity and serum S100 levels as predictive and prognostic biomarkers in high-risk melanoma in the ECOG-intergroup phase II trial E2696 , 2007 .

[55]  R. Scolyer,et al.  Long-Term Protective Effect of Mature DC-LAMP+ Dendritic Cell Accumulation in Sentinel Lymph Nodes Containing Micrometastatic Melanoma , 2007, Clinical Cancer Research.

[56]  J. A. Bernal,et al.  p53 stabilization can be uncoupled from its role in transcriptional activation by loss of PTTG1/securin. , 2007, Journal of biochemistry.

[57]  A. Bosserhoff,et al.  Epigenetic events in malignant melanoma. , 2007, Pigment cell research.

[58]  F. Itoh,et al.  Expression of matrilysin (matrix metalloproteinase‐7) in primary cutaneous and metastatic melanoma , 2007, The British journal of dermatology.

[59]  C. Lebbé,et al.  Clinical value of combined determination of plasma L-DOPA/tyrosine ratio, S100B, MIA and LDH in melanoma. , 2007, European journal of cancer.

[60]  G. Wilson,et al.  Ki-67 expression in melanoma. A potential method of risk assessment for the patient with a positive sentinel node. , 2007, Journal of experimental & clinical cancer research : CR.

[61]  D. Elashoff,et al.  A Comparison of 3 Tumor Markers (MIA, TA90IC, S100B) in Stage III Melanoma Patients , 2007, Cancer investigation.

[62]  J. Utikal,et al.  Serologic and immunohistochemical prognostic biomarkers of cutaneous malignancies , 2007, Archives of Dermatological Research.

[63]  D. Elder,et al.  Predicting sentinel node status in AJCC stage I/II primary cutaneous melanoma , 2006, Cancer.

[64]  H. Pehamberger,et al.  Bcl-2 antisense (oblimersen sodium) plus dacarbazine in patients with advanced melanoma: the Oblimersen Melanoma Study Group. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[65]  F. Baehner,et al.  Prognostic significance of nuclear receptor coactivator-3 overexpression in primary cutaneous melanoma. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[66]  D. Wink,et al.  CD47 Is Necessary for Inhibition of Nitric Oxide-stimulated Vascular Cell Responses by Thrombospondin-1* , 2006, Journal of Biological Chemistry.

[67]  G. Meijer,et al.  Expression and possible role of hPTTG1/securin in cutaneous malignant melanoma , 2006, Modern Pathology.

[68]  Alessandro Ambrosi,et al.  The Prognostic Value of Circulating Tumor Cells in Patients with Melanoma: A Systematic Review and Meta-analysis , 2006, Clinical Cancer Research.

[69]  Steven Gutman,et al.  Opinion: The US Food and Drug Administration perspective on cancer biomarker development , 2006, Nature Reviews Cancer.

[70]  D. Morton,et al.  Estrogen receptor-α methylation predicts melanoma progression , 2006 .

[71]  A. Eggermont,et al.  Gene expression profiling of primary cutaneous melanoma and clinical outcome. , 2006, Journal of the National Cancer Institute.

[72]  J. Gehl,et al.  Elevated serum level of YKL‐40 is an independent prognostic factor for poor survival in patients with metastatic melanoma , 2006, Cancer.

[73]  I. Christensen,et al.  Serum YKL-40 predicts relapse-free and overall survival in patients with American Joint Committee on Cancer stage I and II melanoma. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[74]  D. Nielsen,et al.  Serum YKL-40, A New Prognostic Biomarker in Cancer Patients? , 2006, Cancer Epidemiology Biomarkers & Prevention.

[75]  S. O’Day,et al.  Predictive utility of circulating methylated DNA in serum of melanoma patients receiving biochemotherapy. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[76]  Douglas G Altman,et al.  Reporting recommendations for tumor marker prognostic studies. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[77]  R. Elashoff,et al.  Serial monitoring of circulating melanoma cells during neoadjuvant biochemotherapy for stage III melanoma: outcome prediction in a multicenter trial. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[78]  D G Altman,et al.  REporting recommendations for tumour MARKer prognostic studies (REMARK) , 2005, British journal of cancer.

[79]  I. Dryden,et al.  Serum proteomic fingerprinting discriminates between clinical stages and predicts disease progression in melanoma patients. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[80]  U. Weidle,et al.  Analysis of differential gene expression in human melanocytic tumour lesions by custom made oligonucleotide arrays , 2005, British Journal of Cancer.

[81]  J. Malvehy,et al.  S-100beta and MIA in advanced melanoma in relation to prognostic factors. , 2005, Anticancer research.

[82]  B. Ljung,et al.  The gene expression signatures of melanoma progression , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[83]  Daniel J Sargent,et al.  Clinical trial designs for predictive marker validation in cancer treatment trials. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[84]  A. Viale,et al.  Distinction of desmoplastic melanoma from non-desmoplastic melanoma by gene expression profiling. , 2005, The Journal of investigative dermatology.

[85]  W. Stolz,et al.  Gene expression profile changes between melanoma metastases and their daughter cell lines: implication for vaccination protocols. , 2005, The Journal of investigative dermatology.

[86]  M. Herlyn,et al.  The Role of Altered Cell–Cell Communication in Melanoma Progression , 2003, Journal of Molecular Histology.

[87]  S. Ugurel [Serum markers for melanoma]. , 2005, Der Hautarzt; Zeitschrift fur Dermatologie, Venerologie, und verwandte Gebiete.

[88]  S. Mocellin,et al.  Molecular detection of circulating tumor cells is an independent prognostic factor in patients with high‐risk cutaneous melanoma , 2004, International journal of cancer.

[89]  M. Pierotti,et al.  BRAF alterations are associated with complex mutational profiles in malignant melanoma , 2004, Oncogene.

[90]  B. Kahle,et al.  Diagnosing melanoma patients entering American Joint Committee on Cancer stage IV, C-reactive protein in serum is superior to lactate dehydrogenase , 2004, British Journal of Cancer.

[91]  R. Elashoff,et al.  Prediction of metastatic melanoma in nonsentinel nodes and clinical outcome based on the primary melanoma and the sentinel node , 2004, Modern Pathology.

[92]  D. Morton,et al.  Profiling epigenetic inactivation of tumor suppressor genes in tumors and plasma from cutaneous melanoma patients , 2004, Oncogene.

[93]  R. Scolyer,et al.  The Prognostic Importance of Tumor Mitotic Rate Confirmed in 1317 Patients With Primary Cutaneous Melanoma and Long Follow-Up , 2004, Annals of Surgical Oncology.

[94]  M. Piris,et al.  Progression in cutaneous malignant melanoma is associated with distinct expression profiles: a tissue microarray-based study. , 2004, The American journal of pathology.

[95]  Sing Kai Lo,et al.  Interobserver Reproducibility of Histopathologic Prognostic Variables in Primary Cutaneous Melanomas , 2003, The American journal of surgical pathology.

[96]  William M. Lee,et al.  Serum protein S-100b in acute liver failure: Results of the US acute liver failure study group , 2003 .

[97]  S. Ugurel,et al.  Soluble HLA‐DR is a potent predictive indicator of disease progression in serum from early‐stage melanoma patients , 2002, International journal of cancer.

[98]  Yingdong Zhao,et al.  Prospective molecular profiling of melanoma metastases suggests classifiers of immune responsiveness. , 2002, Cancer research.

[99]  R. Sherwood,et al.  Serum S100 concentrations are not useful in predicting micrometastatic disease in cutaneous malignant melanoma , 2002, The British journal of dermatology.

[100]  Martin F. Mihm,et al.  Final version of the American Joint Committee on Cancer staging system for cutaneous melanoma. , 2001, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[101]  M S Pepe,et al.  Phases of biomarker development for early detection of cancer. , 2001, Journal of the National Cancer Institute.

[102]  S. Ugurel,et al.  Soluble human leukocyte antigen–G serum level is elevated in melanoma patients and is further increased by interferon‐α immunotherapy , 2001 .

[103]  E. Brown,et al.  Integrin-associated protein (CD47) and its ligands. , 2001, Trends in cell biology.

[104]  D. DeMets,et al.  Biomarkers and surrogate endpoints: Preferred definitions and conceptual framework , 2001, Clinical pharmacology and therapeutics.

[105]  U. Leiter,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. , 2001, Anticancer research.

[106]  S. Ugurel,et al.  Increased serum concentration of angiogenic factors in malignant melanoma patients correlates with tumor progression and survival. , 2001, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[107]  J. Manola,et al.  Prognostic factors in metastatic melanoma: a pooled analysis of Eastern Cooperative Oncology Group trials. , 2000, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[108]  A. Bosserhoff,et al.  MIA as a reliable tumor marker in the serum of patients with malignant melanoma. , 2000, Anticancer research.

[109]  R. MacKie,et al.  Rising levels of serum S100 protein precede other evidence of disease progression in patients with malignant melanoma , 2000, The British journal of dermatology.

[110]  J. Cyster,et al.  Chemokines and cell migration in secondary lymphoid organs. , 1999, Science.

[111]  A. Benner,et al.  S100-Beta, melanoma-inhibiting activity, and lactate dehydrogenase discriminate progressive from nonprogressive American Joint Committee on Cancer stage IV melanoma. , 1999, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[112]  Brenner,et al.  Predictive value of serum S100B for monitoring patients with metastatic melanoma during chemotherapy and/or immunotherapy , 1999, The British journal of dermatology.

[113]  A. Hauschild,et al.  S100B Protein Detection in Serum Is a Significant Prognostic Factor in Metastatic Melanoma , 1999, Oncology.

[114]  Schultz,et al.  Clinical and prognostic relevance of serum S‐100β protein in malignant melanoma , 1998 .

[115]  G. Wilson,et al.  Expression of c‐myc oncoprotein represents a new prognostic marker in cutaneous melanoma , 1998, The British journal of surgery.

[116]  R. Sherwood,et al.  Serum S‐100 protein: a potentially useful prognostic marker in cutaneous melanoma , 1997 .

[117]  W. Stolz,et al.  Melanoma-inhibiting activity, a novel serum marker for progression of malignant melanoma. , 1997, Cancer research.

[118]  H. Joller-jemelka,et al.  Serum S100--a marker for disease monitoring in metastatic melanoma. , 1997, Dermatology.

[119]  A. Ganser,et al.  Elevated serum levels of S100 and survival in metastatic malignant melanoma. , 1997, British Journal of Cancer.

[120]  E. Farmer,et al.  Discordance in the histopathologic diagnosis of melanoma and melanocytic nevi between expert pathologists. , 1996, Human pathology.

[121]  L. Hansson,et al.  Prognostic value of serum analyses of S‐100β protein in malignant melanoma , 1996 .

[122]  R. Corona,et al.  Interobserver variability on the histopathologic diagnosis of cutaneous melanoma and other pigmented skin lesions. , 1996, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[123]  Natale Cascinelli,et al.  Prognostic value of tumor infiltrating lymphocytes in the vertical growth phase of primary cutaneous melanoma , 1996, Cancer.

[124]  A. Bosserhoff,et al.  Structure and Promoter Analysis of the Gene Encoding the Human Melanoma-inhibiting Protein MIA (*) , 1996, The Journal of Biological Chemistry.

[125]  L. Hansson,et al.  Prognostic value of serum analyses of S-100 beta protein in malignant melanoma. , 1996, Melanoma research.

[126]  B. Stoffel‐Wagner,et al.  Clinical significance of serum S100 in metastatic malignant melanoma. , 1995, European journal of cancer.

[127]  A. Bosserhoff,et al.  Cloning of a novel malignant melanoma-derived growth-regulatory protein, MIA. , 1994, Cancer research.

[128]  R. Saxton,et al.  S‐100 protein remains a practical marker for melanocytic and other tumours , 1993, Melanoma research.

[129]  U. Bogdahn,et al.  Purification and analysis of growth regulating proteins secreted by a human melanoma cell line , 1992, Melanoma research.

[130]  Horton,et al.  Annals of Oncology , 1991, Springer US.

[131]  A. Halpern,et al.  Model predicting survival in stage I melanoma based on tumor progression. , 1989, Journal of the National Cancer Institute.

[132]  U. Bogdahn,et al.  Autocrine tumor cell growth-inhibiting activities from human malignant melanoma. , 1989, Cancer research.

[133]  G. Bertelli,et al.  LDH in the follow-up of stage I malignant melanoma. , 1988, European journal of cancer & clinical oncology.

[134]  H. Hårdemark,et al.  S-100 protein and neuron-specific enolase in cerebrospinal fluid and serum: markers of cell damage in human central nervous system. , 1987, Stroke.

[135]  A. Cochran,et al.  S‐100 PROTEIN AS A MARKER FOR MELANOCYTIC AND OTHER TUMOURS , 1985, Pathology.

[136]  A. Giuliano,et al.  LDH and melanoma , 1983, Cancer.

[137]  R. Gaynor,et al.  Detection of S‐100 protein as an aid to the identification of melanocytic tumors , 1982, International journal of cancer.

[138]  R. Gaynor,et al.  S100 protein is present in cultured human malignant melanomas , 1980, Nature.

[139]  B. Hill,et al.  Elevation of a serum component in neoplastic disease. , 1954, Cancer research.