Melanoma Update: Diagnostic and Prognostic Factors that Can Effectively Shape and Personalize Management

• Thompson JF , ScolyerRA, KeffordRF: Cutaneous melanoma.Lancet365(9460), 687–701 (2005).
   PubMed Web of Science ®Google Scholar
• Jemal A , SiegelR, WardE, HaoY, XuJ, ThunMJ: Cancer statistics, 2009.CA Cancer J. Clin.59(4), 225–249 (2009).
   PubMed Web of Science ®Google Scholar
• Carlson JA , RossJS, SlominskiAJ: New techniques in dermatopathology that help to diagnose and prognosticate melanoma.Clin. Dermatol.27(1), 75–102 (2009).
   PubMed Web of Science ®Google Scholar
• Beddingfield FC 3rd: The melanoma epidemic: res ipsa loquitur. Oncologist8(5), 459–465 (2003).
   PubMed Web of Science ®Google Scholar
• Seidler AM , PennieML, VeledarE, CullerSD, ChenSC: Economic burden of melanoma in the elderly population: population-based analysis of the surveillance, epidemiology, and end results (SEER)-medicare data.Arch. Dermatol.146(3), 249–256 (2010).
   PubMedGoogle Scholar
• Tawbi HA , KirkwoodJM: Management of metastatic melanoma.Semin. Oncol.34(6), 532–545 (2007).
   PubMed Web of Science ®Google Scholar
• Meyskens FL Jr, Farmer PJ, Yang S, Anton-Culver H: New perspectives on melanoma pathogenesis and chemoprevention. Recent Results Cancer Res.174, 191–195 (2007).
   PubMedGoogle Scholar
• Berwick M , WigginsC: The current epidemiology of cutaneous malignant melanoma.Front. Biosci.11, 1244–1254 (2006).
   PubMed Web of Science ®Google Scholar
• Carlson JA , SlominskiA, LinetteGP, MihmMC Jr, Ross JS: Biomarkers in melanoma: predisposition, screening and diagnosis. Expert Rev. Mol. Diagn.3(2), 163–184 (2003).
   PubMed Web of Science ®Google Scholar
• Armstrong BK , KrickerA: The epidemiology of UV induced skin cancer.J. Photochem. Photobiol. B63(1–3), 8–18 (2001).
   PubMed Web of Science ®Google Scholar
• Curtin JA , BusamK, PinkelD, BastianBC: Somatic activation of KIT in distinct subtypes of melanoma.J. Clin. Oncol.24(26), 4340–4346 (2006).
   PubMed Web of Science ®Google Scholar
• Curtin JA , FridlyandJ, KageshitaTet al. : Distinct sets of genetic alterations in melanoma.N. Engl. J. Med.353(20), 2135–2147 (2005).
   PubMed Web of Science ®Google Scholar
• Bauer J , ButtnerP, MuraliRet al. : BRAF mutations in cutaneous melanoma are independently associated with age, anatomic site of the primary tumor and the degree of solar elastosis at the primary tumor site.Pigment Cell Melanoma Res.24(2), 345–351 (2011).
   PubMed Web of Science ®Google Scholar
• Veierod MB , WeiderpassE, ThornMet al. : A prospective study of pigmentation, sun exposure, and risk of cutaneous malignant melanoma in women.J. Natl Cancer Inst.95(20), 1530–1538 (2003).
   PubMedGoogle Scholar
• Dore JF , PedeuxR, BoniolM, ChignolMC, AutierP: Intermediate-effect biomarkers in prevention of skin cancer.IARC Sci. Publ.154, 81–91 (2001).
   PubMedGoogle Scholar
• Brozyna A , ZbytekB, GraneseJ, CarlsonJA, RossJ, SlominskiA: Mechanism of UV-related carcinogenesis and its contribution to nevi/melanoma.Expert Rev. Dermatol.2(4), 451–469 (2007).
   PubMedGoogle Scholar
• Naldi L , AltieriA, ImbertiGL, GallusS, BosettiC, La Vecchia C: Sun exposure, phenotypic characteristics, and cutaneous malignant melanoma. An analysis according to different clinico-pathological variants and anatomic locations (Italy). Cancer Causes Control16(8), 893–899 (2005).
   PubMed Web of Science ®Google Scholar
• Andersen WK , LabadieRR, BhawanJ: Histopathology of solar lentigines of the face: a quantitative study.J. Am. Acad. Dermatol.36(3 Pt 1), 444–447 (1997).
   PubMed Web of Science ®Google Scholar
• Kossard S : Atypical lentiginous junctional naevi of the elderly and melanoma.Australas J. Dermatol.43(2), 93–101 (2002).
   PubMedGoogle Scholar
• Arumi-Uria M , McnuttNS, FinnertyB: Grading of atypia in nevi: correlation with melanoma risk.Mod. Pathol.16(8), 764–771 (2003).
   PubMed Web of Science ®Google Scholar
• Lee DA , MillerSJ: Nonmelanoma skin cancer.Facial Plast. Surg. Clin. North Am.17(3), 309–324 (2009).
   PubMedGoogle Scholar
• Madan V , LearJT, SzeimiesRM: Non-melanoma skin cancer.Lancet375(9715), 673–685 (2010).
   PubMed Web of Science ®Google Scholar
• Tolleson WH : Human melanocyte biology, toxicology, and pathology.J. Environ. Sci. Health C. Environ. Carcinog. Ecotoxicol. Rev.23(2), 105–161 (2005).
   PubMed Web of Science ®Google Scholar
• Rohwedder A , PhilipsB, MalfetanoJ, KredentserD, CarlsonJA: Vulvar malignant melanoma associated with human papillomavirus DNA: report of two cases and review of literature.Am. J. Dermatopathol.24(3), 230–240 (2002).
   PubMed Web of Science ®Google Scholar
• Rohwedder A , SlominskiA, WolffM, KredentserD, CarlsonJA: Epidermodysplasia verruciformis and cutaneous human papillomavirus DNA, but not genital human papillomavirus DNAs, are frequently detected in vulvar and vaginal melanoma.Am. J. Dermatopathol.29(1), 13–17 (2007).
   PubMed Web of Science ®Google Scholar
• Ragnarsson-Olding BK : Spatial density of primary malignant melanoma in sun-shielded body sites: a potential guide to melanoma genesis.Acta Oncologica50(3), 323–328 (2011).
   PubMed Web of Science ®Google Scholar
• Lipsker D , EngelF, CribierB, VeltenM, HedelinG: Trends in melanoma epidemiology suggest three different types of melanoma.Br. J. Dermatol.157(2), 338–343 (2007).
   PubMed Web of Science ®Google Scholar
• Martorell-Calatayud A , NagoreE, Botella-EstradaRet al. : Defining fast-growing melanomas: reappraisal of epidemiological, clinical, and histological features.Melanoma Res.21(2), 131–138 (2011).
   PubMed Web of Science ®Google Scholar
• Tejera-Vaquerizo A , Barrera-VigoMV, Lopez-NavarroN, Herrera-CeballosE: Growth rate as a prognostic factor in localized invasive cutaneous melanoma.J. Eur. Acad. Dermatol. Venereol.24(2), 147–154 (2010).
   PubMed Web of Science ®Google Scholar
• Criscione VD , WeinstockMA: Melanoma thickness trends in the United States, 1988–2006.J. Invest. Dermatol.130(3), 793–797 (2010).
   PubMed Web of Science ®Google Scholar
• Levell NJ , BeattieCC, ShusterS, GreenbergDC: Melanoma epidemic: a midsummer night‘s dream?Br. J. Dermatol.161(3), 630–634 (2009).
   PubMed Web of Science ®Google Scholar
• Newton Bishop JA , GruisNA: Genetics: what advice for patients who present with a family history of melanoma?Semin. Oncol.34(6), 452–459 (2007).
   PubMed Web of Science ®Google Scholar
• Bishop JN , BatailleV, GavinAet al. : The prevention, diagnosis, referral and management of melanoma of the skin: concise guidelines.Clin. Med.7(3), 283–290 (2007).
   PubMed Web of Science ®Google Scholar
• Singh H , SethiS, RaberM, PetersenLA: Errors in cancer diagnosis: current understanding and future directions.J. Clin. Oncol.25(31), 5009–5018 (2007).
   PubMed Web of Science ®Google Scholar
• Clark WH Jr, ElderDE, GuerryDTet al.: Model predicting survival in stage I melanoma based on tumor progression.J. Natl Cancer Inst.81(24), 1893–1904 (1989).
   PubMed Web of Science ®Google Scholar
• Carlson JA , RossJS, SlominskiAet al. : Molecular diagnostics in melanoma.J. Am. Acad. Dermatol.52(5), 743–775 (2005).
   PubMed Web of Science ®Google Scholar
• Carlson JA , SlominskiA, LinetteGP, MihmMC Jr, Ross JS: Biomarkers in melanoma: staging, prognosis and detection of early metastases. Expert Rev. Mol. Diagn.3(3), 303–330 (2003).
   PubMed Web of Science ®Google Scholar
• Guitart J , LoweL, PiepkornMet al. : Histological characteristics of metastasizing thin melanomas: a case-control study of 43 cases.Arch. Dermatol.138(5), 603–608 (2002).
   PubMedGoogle Scholar
• Cook MG , SpatzA, BrockerEB, RuiterDJ: Identification of histological features associated with metastatic potential in thin (<1.0 mm) cutaneous melanoma with metastases. A study on behalf of the EORTC Melanoma Group.J. Pathol.197(2), 188–193 (2002).
   PubMed Web of Science ®Google Scholar
• Mckinnon JG , YuXQ, MccarthyWH, ThompsonJF: Prognosis for patients with thin cutaneous melanoma: long-term survival data from New South Wales Central Cancer Registry and the Sydney Melanoma Unit.Cancer98(6), 1223–1231 (2003).
   PubMed Web of Science ®Google Scholar
• Gimotty PA , BotbylJ, SoongSJ, GuerryD: A population-based validation of the American Joint Committee on cancer melanoma staging system.J. Clin. Oncol.23(31), 8065–8075 (2005).
   PubMed Web of Science ®Google Scholar
• Balch CM , BuzaidAC, SoongSJet al. : Final version of the American Joint Committee on cancer staging system for cutaneous melanoma.J. Clin. Oncol.19(16), 3635–3648 (2001).
   PubMed Web of Science ®Google Scholar
• Meier F , WillS, EllwangerUet al. : Metastatic pathways and time courses in the orderly progression of cutaneous melanoma.Br. J. Dermatol.147(1), 62–70 (2002).
   PubMed Web of Science ®Google Scholar
• Li Y , McclayEF: Systemic chemotherapy for the treatment of metastatic melanoma.Semin.Oncol.29(5), 413–426 (2002).
   PubMed Web of Science ®Google Scholar
• Lorigan P , EisenT, HauschildA: Systemic therapy for metastatic malignant melanoma – from deeply disappointing to bright future?Exp. Dermatol.17(5), 383–394 (2008).
   PubMed Web of Science ®Google Scholar
• Linette GP , CarlsonJA, SlominskiA, MihmMC, RossJS: Biomarkers in melanoma: stage III and IV disease.Expert Rev. Mol. Diagn.5(1), 65–74 (2005).
   PubMed Web of Science ®Google Scholar
• Davies MA , GershenwaldJE: Targeted therapy for melanoma: a primer.Surg. Oncol. Clin. N. Am.20(1), 165–180 (2011).
   PubMed Web of Science ®Google Scholar
• Bielas JH , LoebLA: Mutator phenotype in cancer: timing and perspectives.Environ. Mol. Mutagen45(2–3), 206–213 (2005).
   PubMed Web of Science ®Google Scholar
• Hanahan D , WeinbergRA: The hallmarks of cancer.Cell100(1), 57–70 (2000).
   PubMed Web of Science ®Google Scholar
• Nowell PC : Tumor progression: a brief historical perspective.Semin. Cancer Biol.12(4), 261–266 (2002).
   PubMed Web of Science ®Google Scholar
• Negrini S , GorgoulisVG, HalazonetisTD: Genomic instability – an evolving hallmark of cancer.Nat. Rev. Mol. Cell Biol.11(3), 220–228 (2010).
   PubMed Web of Science ®Google Scholar
• Hussein MR , WoodGS: Microsatellite instability and its relevance to cutaneous tumorigenesis.J. Cutan. Pathol.29(5), 257–267 (2002).
   PubMed Web of Science ®Google Scholar
• Cahill DP , KinzlerKW, VogelsteinB, LengauerC: Genetic instability and darwinian selection in tumours.Trends Cell Biol.9(12), M57–M60 (1999).
   PubMed Web of Science ®Google Scholar
• Ushijima T : Epigenetic field for cancerization.J. Biochem. Mol. Biol.40(2), 142–150 (2007).
   PubMedGoogle Scholar
• Lengauer C , KinzlerKW, VogelsteinB: Genetic instabilities in human cancers.Nature396(6712), 643–649 (1998).
   PubMed Web of Science ®Google Scholar
• Duesberg PH : Are cancers dependent on oncogenes or on aneuploidy?Cancer Genet. Cytogenet.143(1), 89–91 (2003).
   PubMedGoogle Scholar
• Michor F , IwasaY, VogelsteinB, LengauerC, NowakMA: Can chromosomal instability initiate tumorigenesis?Semin. Cancer Biol.15(1), 43–49 (2005).
   PubMed Web of Science ®Google Scholar
• Pleasance ED , CheethamRK, StephensPJet al. : A comprehensive catalogue of somatic mutations from a human cancer genome.Nature463(7278), 191–196 (2010).
   PubMed Web of Science ®Google Scholar
• Pleasance ED , StephensPJ, O‘mearaSet al. : A small-cell lung cancer genome with complex signatures of tobacco exposure.Nature463(7278), 184–190 (2010).
   PubMed Web of Science ®Google Scholar
• Loeb LA , BielasJH, BeckmanRA: Cancers exhibit a mutator phenotype: clinical implications.Cancer Res.68(10), 3551–3557; discussion 3557 (2008).
   PubMed Web of Science ®Google Scholar
• Schollnberger H , BeerenwinkelN, HoogenveenR, VineisP: Cell selection as driving force in lung and colon carcinogenesis.Cancer Res.70(17), 6797–6803 (2010).
   PubMed Web of Science ®Google Scholar
• Bozic I , AntalT, OhtsukiHet al. : Accumulation of driver and passenger mutations during tumor progression.Proc. Natl Acad. Sci. USA107(43), 18545–18550 (2010).
   PubMed Web of Science ®Google Scholar
• Rubin H : Fields and field cancerization: the preneoplastic origins of cancer: asymptomatic hyperplastic fields are precursors of neoplasia, and their progression to tumors can be tracked by saturation density in culture.Bioessays33(3), 224–231 (2011).
   PubMed Web of Science ®Google Scholar
• Carlson JA , MurphyM, SlominskiA, WilsonVL: Evidence of skin field cancerization. In: Field Cancerization: Basic Science and Clinical Applications, Dakubo G (Ed.). Nova Science Publishers, Hauppauge, New York, NY, USA (2011).
   Google Scholar
• Kaur P , MulvaneyM, CarlsonJA: Basal cell carcinoma progression correlates with host immune response and stromal alterations: a histologic analysis.Am. J. Dermatopathol.28(4), 293–307 (2006).
   PubMed Web of Science ®Google Scholar
• Carlson JA , HealyK, TranTAet al. : Chromosome 17 aneusomy detected by fluorescence in situ hybridization in vulvar squamous cell carcinomas and synchronous vulvar skin.Am. J. Pathol.157(3), 973–983 (2000).
   PubMed Web of Science ®Google Scholar
• Carlson JA , AminS, MalfetanoJet al. : Concordant p53 and mdm-2 protein expression in vulvar squamous cell carcinoma and adjacent lichen sclerosus.Appl. Immunohistochem. Mol. Morphol.9(2), 150–163 (2001).
   PubMedGoogle Scholar
• Padilla RS , SebastianS, JiangZ, NindlI, LarsonR: Gene expression patterns of normal human skin, actinic keratosis, and squamous cell carcinoma: a spectrum of disease progression.Arch. Dermatol.146(3), 288–293 (2010).
   PubMedGoogle Scholar
• Armitage P , DollR: The age distribution of cancer and a multi-stage theory of carcinogenesis.Br. J. Cancer8(1), 1–12 (1954).
   PubMed Web of Science ®Google Scholar
• Ashton KJ , CarlessMA, GriffithsLR: Cytogenetic alterations in nonmelanoma skin cancer: a review.Genes Chromosomes Cancer43(3), 239–248 (2005).
   PubMed Web of Science ®Google Scholar
• Boukamp P : Non-melanoma skin cancer: what drives tumor development and progression?Carcinogenesis26(10), 1657–1667 (2005).
   PubMed Web of Science ®Google Scholar
• Blokx WA , Van Dijk MC, Ruiter DJ: Molecular cytogenetics of cutaneous melanocytic lesions – diagnostic, prognostic and therapeutic aspects. Histopathology56(1), 121–132 (2010).
   PubMed Web of Science ®Google Scholar
• Dadzie OE , YangS, EmleyA, KeadyM, BhawanJ, MahalingamM: RAS and RAF mutations in banal melanocytic aggregates contiguous with primary cutaneous melanoma: clues to melanomagenesis.Br. J. Dermatol.160(2), 368–375 (2009).
   PubMed Web of Science ®Google Scholar
• Zabierowski SE , HerlynM: Melanoma stem cells: the dark seed of melanoma.J. Clin. Oncol.26(17), 2890–2894 (2008).
   PubMed Web of Science ®Google Scholar
• Tucker MA , FraserMC, GoldsteinAMet al. : A natural history of melanomas and dysplastic nevi: an atlas of lesions in melanoma-prone families.Cancer94(12), 3192–3209 (2002).
   PubMed Web of Science ®Google Scholar
• Kelly JW , YeatmanJM, RegaliaC, MasonG, HenhamAP: A high incidence of melanoma found in patients with multiple dysplastic naevi by photographic surveillance.Med. J. Aust.167(4), 191–194. (1997).
   PubMed Web of Science ®Google Scholar
• Sell S : Cancer stem cells and differentiation therapy.Tumour Biol.27(2), 59–70 (2006).
   PubMedGoogle Scholar
• Bissell MJ , HinesWC: Why don‘t we get more cancer? A proposed role of the microenvironment in restraining cancer progression.Nat. Med.17(3), 320–329 (2011).
   PubMed Web of Science ®Google Scholar
• Bastian BC , LeboitPE, HammH, BrockerEB, PinkelD: Chromosomal gains and losses in primary cutaneous melanomas detected by comparative genomic hybridization.Cancer Res.58(10), 2170–2175 (1998).
   PubMed Web of Science ®Google Scholar
• Carless MA , GriffithsLR: Cytogenetics of melanoma and nonmelanoma skin cancer.Adv. Exp. Med. Biol.624, 227–240 (2008).
   PubMed Web of Science ®Google Scholar
• Crotty K , MccarthySW, MihmM Jr: The histologic diagnosis and classification of melanoma. In: Textbook of Melanoma. Thompson JF, Morton DL, Kroon BB (Eds). Martin Dunitz, London, UK (2004).
   Google Scholar
• Sagebiel RW : Pigmented lesion pathology: the specimen and its report. A personal and probably biased approach.Pathology (Phila.)2(2), 281–298 (1994).
   PubMedGoogle Scholar
• Banerjee SS , HarrisM: Morphological and immunophenotypic variations in malignant melanoma.Histopathology36(5), 387–402 (2000).
   PubMed Web of Science ®Google Scholar
• Kirkham N : Optimal handling and criteria for melanoma diagnosis.Histopathology37(5), 467–469 (2000).
   PubMed Web of Science ®Google Scholar
• Cerroni L , KerlH: Tutorial on melanocytic lesions.Am. J. Dermatopathol.23(3), 237–241 (2001).
   PubMedGoogle Scholar
• Shoo BA , SagebielRW, Kashani-SabetM: Discordance in the histopathologic diagnosis of melanoma at a melanoma referral center.J. Am. Acad. Dermatol.62(5), 751–756 (2010).
   PubMed Web of Science ®Google Scholar
• Jackson R : Malignant melanoma: a review of 75 malpractice cases.Int. J. Dermatol.36(7), 497–498 (1997).
   PubMed Web of Science ®Google Scholar
• Troxel DB : Pitfalls in the diagnosis of malignant melanoma: findings of a risk management panel study.Am. J. Surg. Pathol.27(9), 1278–1283 (2003).
   PubMed Web of Science ®Google Scholar
• Van Dijk MC , AbenKK, Van HeesFet al.: Expert review remains important in the histopathological diagnosis of cutaneous melanocytic lesions.Histopathology52(2), 139–146 (2008).
   PubMed Web of Science ®Google Scholar
• Cerroni L , BarnhillR, ElderDet al. : Melanocytic tumors of uncertain malignant potential: results of a tutorial held at the XXIX symposium of the International Society of Dermatopathology in Graz, October 2008.Am. J. Surg. Pathol.34(3), 314–326 (2010).
   PubMed Web of Science ®Google Scholar
• Barnhill RL : The Spitzoid lesion: rethinking Spitz tumors, atypical variants, ‘Spitzoid melanoma‘ and risk assessment.Mod. Pathol.19(Suppl. 2), S21–S33 (2006).
   PubMed Web of Science ®Google Scholar
• Wechsler J , Bastuji-GarinS, SpatzAet al. : Reliability of the histopathologic diagnosis of malignant melanoma in childhood.Arch. Dermatol.138(5), 625–628 (2002).
   PubMedGoogle Scholar
• Brochez L , VerhaegheE, GrosshansEet al. : Inter-observer variation in the histopathological diagnosis of clinically suspicious pigmented skin lesions.J. Pathol.196(4), 459–466 (2002).
   PubMed Web of Science ®Google Scholar
• Lodha S , SaggarS, CelebiJT, SilversDN: Discordance in the histopathologic diagnosis of difficult melanocytic neoplasms in the clinical setting.J. Cutan. Pathol.35(4), 349–352 (2008).
   PubMed Web of Science ®Google Scholar
• Scolyer RA , ShawHM, ThompsonJFet al. : Interobserver reproducibility of histopathologic prognostic variables in primary cutaneous melanomas.Am. J. Surg. Pathol.27(12), 1571–1576 (2003).
   PubMed Web of Science ®Google Scholar
• Elder DE , MurphyGF: Melanocytic Tumors of the Skin. (3rd Edition). American Registry of Pathology, Washington, DC, USA (1991).
   Google Scholar
• Slater DN : Melanocytic intra-epidermal neoplasia (MIN).Histopathology30(2), 195–197 (1997).
   PubMedGoogle Scholar
• Elder DE , XuX: The approach to the patient with a difficult melanocytic lesion.Pathology36(5), 428–434 (2004).
   PubMed Web of Science ®Google Scholar
• Bastian BC : Molecular genetics of melanocytic neoplasia: practical applications for diagnosis.Pathology36(5), 458–461 (2004).
   PubMed Web of Science ®Google Scholar
• Bauer J , BastianBC: Distinguishing melanocytic nevi from melanoma by DNA copy number changes: comparative genomic hybridization as a research and diagnostic tool.Dermatol. Ther.19(1), 40–49 (2006).
   PubMed Web of Science ®Google Scholar
• Piris A , MihmMC Jr: Progress in melanoma histopathology and diagnosis. Hematol. Oncol. Clin. North Am.23(3), 467–480 (2009).
   PubMed Web of Science ®Google Scholar
• Ruiter D , MooiW, Van Muijen GN, Cochran AJ: Immunohistochemistry and special diagnostic techniques. In: Textbook of Melanoma. Thompson JF, Morton DL, Kroon BB (Eds). Martin Dunitz, London, UK, 129–147 (2004).
   Google Scholar
• Busam KJ : The use and application of special techniques in assessing melanocytic tumours.Pathology36(5), 462–469 (2004).
   PubMed Web of Science ®Google Scholar
• Tuthill RJ , ReedRJ: Failure of senescence in the dysplasia-melanoma sequence: demonstration using a tissue microarray and a revised paradigm for melanoma.Semin. Oncol.34(6), 467–475 (2007).
   PubMed Web of Science ®Google Scholar
• Gerami P , JewellSS, MorrisonLEet al. : Fluorescence in situ hybridization (FISH) as an ancillary diagnostic tool in the diagnosis of melanoma.Am. J. Surg. Pathol.33(8), 1146–1156 (2009).
   PubMed Web of Science ®Google Scholar
• Hammock L , CohenC, CarlsonGet al. : Chromogenic in situ hybridization analysis of melastatin mRNA expression in melanomas from American Joint Committee on Cancer stage I and II patients with recurrent melanoma.J. Cutan. Pathol.33(9), 599–607 (2006).
   PubMed Web of Science ®Google Scholar
• Takata M , SuzukiT, AnsaiSet al. : Genome profiling of melanocytic tumors using multiplex ligation-dependent probe amplification (MLPA): its usefulness as an adjunctive diagnostic tool for melanocytic tumors.J. Dermatol. Sci.40(1), 51–57 (2005).
   PubMed Web of Science ®Google Scholar
• Itakura E , HuangRR, WenDR, PaulE, WunschPH, CochranAJ: RT in situ PCR detection of MART-1 and TRP-2 mRNA in formalin-fixed, paraffin-embedded tissues of melanoma and nevi.Mod. Pathol.21(3), 326–333 (2008).
   PubMed Web of Science ®Google Scholar
• Gjerdrum LM , AbrahamsenHN, VillegasB, SorensenBS, SchmidtH, Hamilton-DutoitSJ: The influence of immunohistochemistry on mRNA recovery from microdissected frozen and formalin-fixed, paraffin-embedded sections.Diagn. Mol. Pathol.13(4), 224–233 (2004).
   PubMedGoogle Scholar
• Van Dijk MC , RomboutPD, MooiWJet al. : Allelic imbalance in the diagnosis of benign, atypical and malignant Spitz tumours.J. Pathol.197(2), 170–178 (2002).
   PubMed Web of Science ®Google Scholar
• Dadzie OE , NeatM, EmleyA, BhawanJ, MahalingamM: Molecular diagnostics-an emerging frontier in dermatopathology.Am. J. Dermatopathol.33(1), 1–13 (2011).
   PubMed Web of Science ®Google Scholar
• Wachsman W , MorhennV, PalmerTet al. : Non-invasive genomic detection of melanoma.Br. J. Dermatol.164(4), 797–806 (2011).
   PubMed Web of Science ®Google Scholar
• Slominski A : Coming of age of melanogenesis-related proteins.Arch. Pathol. Lab. Med.126(7), 775–777 (2002).
   PubMed Web of Science ®Google Scholar
• Ohsie SJ , SarantopoulosGP, CochranAJ, BinderSW: Immunohistochemical characteristics of melanoma.J. Cutan. Pathol.35(5), 433–444 (2008).
   PubMed Web of Science ®Google Scholar
• Heintz PW , WhiteCR Jr: Diagnosis: atypical fibroxanthoma or not? Evaluating spindle cell malignancies on sun damaged skin: a practical approach. Semin. Cutan. Med. Surg.18(1), 78–83 (1999).
   PubMed Web of Science ®Google Scholar
• Carlson JA , DickersinGR, SoberAJ, BarnhillRL: Desmoplastic neurotropic melanoma. A clinicopathologic analysis of 28 cases.Cancer75(2), 478–494 (1995).
   PubMed Web of Science ®Google Scholar
• Kanik AB , YaarM, BhawanJ: p75 nerve growth factor receptor staining helps identify desmoplastic and neurotropic melanoma.J. Cutan. Pathol.23(3), 205–210 (1996).
   PubMed Web of Science ®Google Scholar
• Fanburg-Smith JC , MiettinenM: Low-affinity nerve growth factor receptor (p75) in dermatofibrosarcoma protuberans and other nonneural tumors: a study of 1,150 tumors and fetal and adult normal tissues.Hum. Pathol.32(9), 976–983 (2001).
   PubMed Web of Science ®Google Scholar
• Boyle JL , HauptHM, SternJB, MulthauptHA: Tyrosinase expression in malignant melanoma, desmoplastic melanoma, and peripheral nerve tumors.Arch. Pathol. Lab. Med.126(7), 816–822 (2002).
   PubMed Web of Science ®Google Scholar
• Fullen DR , GarrisiAJ, SandersD, ThomasD: Expression of S100A6 protein in a broad spectrum of cutaneous tumors using tissue microarrays.J. Cutan. Pathol.35(Suppl. 2), 28–34 (2008).
   PubMed Web of Science ®Google Scholar
• 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.32(8), 475–481 (2000).
   PubMedGoogle Scholar
• Miettinen M , FernandezM, FranssilaK, GatalicaZ, LasotaJ, Sarlomo-RikalaM: Microphthalmia transcription factor in the immunohistochemical diagnosis of metastatic melanoma: comparison with four other melanoma markers.Am. J. Surg. Pathol.25(2), 205–211. (2001).
   PubMed Web of Science ®Google Scholar
• Mangini J , LiN, BhawanJ: Immunohistochemical markers of melanocytic lesions: a review of their diagnostic usefulness.Am. J. Dermatopathol.24(3), 270–281 (2002).
   PubMed Web of Science ®Google Scholar
• Granter SR , WeilbaecherKN, QuigleyC, FisherDE: Role for microphthalmia transcription factor in the diagnosis of metastatic malignant melanoma.Appl. Immunohistochem. Mol. Morphol.10(1), 47–51 (2002).
   PubMedGoogle Scholar
• Slominski A , TobinD, ShibaharaS, WortsmanJ: Melanin pigmentation in mammalian skin and its hormonal regulation.Physiol. Rev.84(4), 1155–228 (2004).
   PubMed Web of Science ®Google Scholar
• Sheffield MV , YeeH, DorvaultCCet al. : Comparison of five antibodies as markers in the diagnosis of melanoma in cytologic preparations.Am. J. Clin. Pathol.118(6), 930–936 (2002).
   PubMed Web of Science ®Google Scholar
• Blessing K , SandersDS, GrantJJ: Comparison of immunohistochemical staining of the novel antibody melan-A with S100 protein and HMB-45 in malignant melanoma and melanoma variants.Histopathology32(2), 139–146 (1998).
   PubMed Web of Science ®Google Scholar
• Plaza JA , SusterD, Perez-MontielD: Expression of immunohistochemical markers in primary and metastatic malignant melanoma: a comparative study in 70 patients using a tissue microarray technique.Appl. Immunohistochem. Mol. Morphol.15(4), 421–425 (2007).
   PubMedGoogle Scholar
• Mcnutt NS , UrmacherC, HakimianJ, HossDM, LugoJ: Nevoid malignant melanoma: morphologic patterns and immunohistochemical reactivity.J. Cutan. Pathol.22(6), 502–517 (1995).
   PubMed Web of Science ®Google Scholar
• Crotty KA , ScolyerRA, LiL, PalmerAA, WangL, MccarthySW: Spitz naevus versus Spitzoid melanoma: when and how can they be distinguished?Pathology34(1), 6–12 (2002).
   PubMed Web of Science ®Google Scholar
• Li LX , CrottyKA, PalmerAAet al. : Differentiating benign nevi from malignant melanoma using DNA microdensitometry and karyometry and maturation: a zonal comparison, correlation and multivariate analysis.Anal. Quant. Cytol. Histol.24(4), 234–243 (2002).
   PubMedGoogle Scholar
• Ribe A , McnuttNS: S100A6 protein expression is different in Spitz nevi and melanomas.Mod. Pathol.16(5), 505–511 (2003).
   PubMed Web of Science ®Google Scholar
• Timar J , UdvarhelyiN, BanfalviT, GildeK, OroszZ: Accuracy of the determination of S100B protein expression in malignant melanoma using polyclonal or monoclonal antibodies.Histopathology44(2), 180–184 (2004).
   PubMed Web of Science ®Google Scholar
• Bottoni U , IzzoP, RichettaAet al. : S100 serum level: a tumour marker for metastatic melanoma.Melanoma Res.13(4), 427–429 (2003).
   PubMed Web of Science ®Google Scholar
• Bouwhuis MG , SuciuS, KruitWet al. : Prognostic value of serial blood S100B determinations in stage IIB-III melanoma patients: a corollary study to EORTC trial 18952.Eur. J. Cancer47(3), 361–368 (2011).
   PubMed Web of Science ®Google Scholar
• Puri PK , FerringerTC, TylerWB, WilsonML, KirchnerHL, ElstonDM: Statistical analysis of the concordance of immunohistochemical stains with the final diagnosis in spitzoid neoplasms.Am. J. Dermatopathol.33(1), 72–77 (2011).
   PubMed Web of Science ®Google Scholar
• Hendi A , BrodlandDG, ZitelliJA: Melanocytes in long-standing sun-exposed skin: quantitative analysis using the MART-1 immunostain.Arch. Dermatol.142(7), 871–876 (2006).
   PubMedGoogle Scholar
• Brozyna AA , JozwickiW, JanjetovicZ, SlominskiAT: Expression of vitamin D receptor decreases during progression of pigmented skin lesions.Hum. Pathol.42(5), 618–631 (2011).
   PubMed Web of Science ®Google Scholar
• Pinczewski J , SlominskiA: The potential role of vitamin D in the progression of benign and malignant melanocytic neoplasms.Exp. Dermatol.19(10), 860–864 (2010).
   PubMed Web of Science ®Google Scholar
• Itakura E , HuangRR, WenDR, PaulE, WunschPH, CochranAJ: IL-10 expression by primary tumor cells correlates with melanoma progression from radial to vertical growth phase and development of metastatic competence.Mod. Pathol. DOI:10.1038/modpathol.2011.5 (2011) (Epub ahead of print).
   PubMedGoogle Scholar
• Wilsher M , CheeralaB: WT1 as a complementary marker of malignant melanoma: an immunohistochemical study of whole sections.Histopathology51(5), 605–610 (2007).
   PubMed Web of Science ®Google Scholar
• Kashani-Sabet M , RangelJ, TorabianSet al. : A multi-marker assay to distinguish malignant melanomas from benign nevi.Proc. Natl Acad. Sci. USA106(15), 6268–6272 (2009).
   PubMed Web of Science ®Google Scholar
• Jones PA , BaylinSB: The fundamental role of epigenetic events in cancer.Nat. Rev. Genet.3(6), 415–428 (2002).
   PubMed Web of Science ®Google Scholar
• Alonso SR , OrtizP, PollanMet al. : Progression in cutaneous malignant melanoma is associated with distinct expression profiles: a tissue microarray-based study.Am. J. Pathol.164(1), 193–203 (2004).
   PubMed Web of Science ®Google Scholar
• Hilliard NJ , KrahlD, SellheyerK: p16 expression differentiates between desmoplastic Spitz nevus and desmoplastic melanoma.J. Cutan. Pathol.36(7), 753–759 (2009).
   PubMed Web of Science ®Google Scholar
• Mu XC , TranTA, RossJS, CarlsonJA: Topoisomerase II-α expression in melanocytic nevi and malignant melanoma.J. Cutan. Pathol.27(5), 242–248 (2000).
   PubMed Web of Science ®Google Scholar
• Rieger E , Hofmann-WellenhofR, SoyerHPet al. : Comparison of proliferative activity as assessed by proliferating cell nuclear antigen (PCNA) and Ki-67 monoclonal antibodies in melanocytic skin lesions. A quantitative immunohistochemical study.J. Cutan. Pathol.20(3), 229–236 (1993).
   PubMed Web of Science ®Google Scholar
• Sparrow LE , EnglishDR, TaranJM, HeenanPJ: Prognostic significance of MIB-1 proliferative activity in thin melanomas and immunohistochemical analysis of MIB-1 proliferative activity in melanocytic tumors.Am. J. Dermatopathol.20(1), 12–16 (1998).
   PubMed Web of Science ®Google Scholar
• Bergman R , MalkinL, SaboE, KernerH: MIB-1 monoclonal antibody to determine proliferative activity of Ki-67 antigen as an adjunct to the histopathologic differential diagnosis of Spitz nevi.J. Am. Acad. Dermatol.44(3), 500–504 (2001).
   PubMed Web of Science ®Google Scholar
• George E , PolissarNL, WickM: Immunohistochemical evaluation of p16INK4A, E-cadherin, and cyclin D1 expression in melanoma and Spitz tumors.Am. J. Clin. Pathol.133(3), 370–379 (2010).
   PubMed Web of Science ®Google Scholar
• Maldonado JL , TimmermanL, FridlyandJ, BastianBC: Mechanisms of cell-cycle arrest in Spitz nevi with constitutive activation of the MAP-kinase pathway.Am. J. Pathol.164(5), 1783–1787 (2004).
   PubMed Web of Science ®Google Scholar
• Korabiowska M , BetkeH, KellnerS, StachuraJ, SchauerA: Differential expression of growth arrest, DNA damage genes and tumour suppressor gene p53 in naevi and malignant melanomas.Anticancer Res.17(5A), 3697–3700 (1997).
   PubMed Web of Science ®Google Scholar
• Zucman J , MelotT, DesmazeCet al. : Combinatorial generation of variable fusion proteins in the Ewing family of tumours.Embo J.12(12), 4481–4487 (1993).
   PubMed Web of Science ®Google Scholar
• Bastian BC , XiongJ, FriedenIJet al. : Genetic changes in neoplasms arising in congenital melanocytic nevi: differences between nodular proliferations and melanomas.Am. J. Pathol.161(4), 1163–1169 (2002).
   PubMed Web of Science ®Google Scholar
• Maitra A , GazdarAF, MooreTO, MooreAY: Loss of heterozygosity analysis of cutaneous melanoma and benign melanocytic nevi: laser capture microdissection demonstrates clonal genetic changes in acquired nevocellular nevi.Hum. Pathol.33(2), 191–197 (2002).
   PubMed Web of Science ®Google Scholar
• Udart M , UtikalJ, KrahnGM, PeterRU: Chromosome 7 aneusomy. A marker for metastatic melanoma? Expression of the epidermal growth factor receptor gene and chromosome 7 aneusomy in nevi, primary malignant melanomas and metastases.Neoplasia3(3), 245–254 (2001).
   PubMed Web of Science ®Google Scholar
• Korabiowska M , BrinckU, KotthausI, BergerH, DroeseM: Analysis of the DNA content in the progression of recurrent and metastatic melanomas.Anticancer Res.20(4), 2791–2794 (2000).
   PubMed Web of Science ®Google Scholar
• Bastian BC , OlshenAB, LeboitPE, PinkelD: Classifying melanocytic tumors based on DNA copy number changes.Am. J. Pathol.163(5), 1765–1770 (2003).
   PubMed Web of Science ®Google Scholar
• Leech SN , BellH, LeonardNet al. : Neonatal giant congenital nevi with proliferative nodules: a clinicopathologic study and literature review of neonatal melanoma.Arch. Dermatol.140(1), 83–88 (2004).
   PubMedGoogle Scholar
• Scolyer RA , PrietoVG: Melanoma pathology: important issues for clinicians involved in the multidisciplinary care of melanoma patients.Surg. Oncol. Clin. N. Am.20(1), 19–37 (2011).
   PubMed Web of Science ®Google Scholar
• Newman MD , LertsburapaT, MirzabeigiM, MafeeM, GuitartJ, GeramiP: Fluorescence in situ hybridization as a tool for microstaging in malignant melanoma.Mod. Pathol.22(8), 989–995 (2009).
   PubMed Web of Science ®Google Scholar
• Newman MD , MirzabeigiM, GeramiP: Chromosomal copy number changes supporting the classification of lentiginous junctional melanoma of the elderly as a subtype of melanoma.Mod. Pathol.22(9), 1258–1262 (2009).
   PubMed Web of Science ®Google Scholar
• Pouryazdanparast P , NewmanM, MafeeM, HaghighatZ, GuitartJ, GeramiP: Distinguishing epithelioid blue nevus from blue nevus-like cutaneous melanoma metastasis using fluorescence in situ hybridization.Am. J. Surg. Pathol.33(9), 1396–1400 (2009).
   PubMed Web of Science ®Google Scholar
• Dalton SR , GeramiP, KolaitisNAet al. : Use of fluorescence in situ hybridization (FISH) to distinguish intranodal nevus from metastatic melanoma.Am. J. Surg. Pathol.34(2), 231–237 (2010).
   PubMed Web of Science ®Google Scholar
• Gerami P , BarnhillRL, BeilfussBA, LeboitP, SchneiderP, GuitartJ: Superficial melanocytic neoplasms with pagetoid melanocytosis: a study of interobserver concordance and correlation with FISH.Am. J. Surg. Pathol.34(6), 816–821 (2010).
   PubMed Web of Science ®Google Scholar
• Gerami P , MafeeM, LurtsbarapaT, GuitartJ, HaghighatZ, NewmanM: Sensitivity of fluorescence in situ hybridization for melanoma diagnosis using RREB1, MYB, Cep6, and 11q13 probes in melanoma subtypes.Arch. Dermatol.146(3), 273–278 (2010).
   PubMedGoogle Scholar
• Gerami P , PouryazdanparastP, VemulaS, BastianBC: Molecular analysis of a case of nevus of ota showing progressive evolution to melanoma with intermediate stages resembling cellular blue nevus.Am. J. Dermatopathol.32(3), 301–305 (2010).
   PubMed Web of Science ®Google Scholar
• Isaac AK , LertsburapaT, Pathria Mundi J, Martini M, Guitart J, Gerami P: Polyploidy in spitz nevi: a not uncommon karyotypic abnormality identifiable by fluorescence in situ hybridization. Am. J. Dermatopathol.32(2), 144–148 (2010).
   PubMed Web of Science ®Google Scholar
• Gammon B , BeilfussB, GuitartJ, BusamKJ, GeramiP: Fluorescence in situ hybridization for distinguishing cellular blue nevi from blue nevus-like melanoma.J. Cutan. Pathol.38(4), 335–341 (2011).
   PubMed Web of Science ®Google Scholar
• Busam KJ , FangY, JhanwarSC, PulitzerMP, MarrB, AbramsonDH: Distinction of conjunctival melanocytic nevi from melanomas by fluorescence in situ hybridization.J. Cutan. Pathol.37(2), 196–203 (2010).
   PubMed Web of Science ®Google Scholar
• Gerami P , BeilfussB, HaghighatZ, FangY, JhanwarS, BusamKJ: Fluorescence in situ hybridization as an ancillary method for the distinction of desmoplastic melanomas from sclerosing melanocytic nevi.J. Cutan. Pathol.38(4), 329–334 (2011).
   PubMed Web of Science ®Google Scholar
• Vergier B , Prochazkova-CarlottiM, De La FouchardiereAet al.: Fluorescence in situ hybridization, a diagnostic aid in ambiguous melanocytic tumors: European study of 113 cases.Mod. Pathol.24(5), 613–623 (2011).
   PubMed Web of Science ®Google Scholar
• Gaiser T , KutznerH, PalmedoGet al. : Classifying ambiguous melanocytic lesions with FISH and correlation with clinical long-term follow up.Mod. Pathol.23(3), 413–419 (2010).
   PubMed Web of Science ®Google Scholar
• Massi D , CesinaroAM, TomasiniCet al. : Atypical Spitzoid melanocytic tumors: a morphological, mutational, and FISH analysis.J. Am. Acad. Dermatol.64(5), 919–935 (2011).
   PubMed Web of Science ®Google Scholar
• North JP , KageshitaT, PinkelD, LeboitPE, BastianBC: Distribution and significance of occult intraepidermal tumor cells surrounding primary melanoma.J. Invest. Dermatol.128(8), 2024–2030 (2008).
   PubMed Web of Science ®Google Scholar
• Gerami P , JewellSS, PouryazdanparastPet al. : Copy number gains in 11q13 and 8q34 are highly linked to prognosis in cutaneous malignant melanoma.J. Mol. Diagn.13(3), 352–358 (2011).
   PubMed Web of Science ®Google Scholar
• Dickson PV , GershenwaldJE: Staging and prognosis of cutaneous melanoma.Surg. Oncol. Clin. N. Am.20(1), 1–17 (2011).
   PubMed Web of Science ®Google Scholar
• Balch CM , GershenwaldJE, SoongSJet al. : Final version of 2009 AJCC melanoma staging and classification.J. Clin. Oncol.27(36), 6199–6206 (2009).
   PubMed Web of Science ®Google Scholar
• Cormier JN , XingY, FengLet al. : Metastatic melanoma to lymph nodes in patients with unknown primary sites.Cancer106(9), 2012–2020 (2006).
   PubMed Web of Science ®Google Scholar
• Lee CC , FariesMB, WanekLA, MortonDL: Improved survival after lymphadenectomy for nodal metastasis from an unknown primary melanoma.J. Clin. Oncol.26(4), 535–541 (2008).
   PubMed Web of Science ®Google Scholar
• Pfeil AF , LeiterU, BuettnerPGet al. : Melanoma of unknown primary is correctly classified by the AJCC melanoma classification from 2009.Melanoma Res.21(3), 228–234 (2011).
   PubMed Web of Science ®Google Scholar
• Grob JJ , RichardMA, GouvernetJet al. : The kinetics of the visible growth of a primary melanoma reflects the tumor aggressiveness and is an independent prognostic marker: a prospective study.Int. J. Cancer102(1), 34–38 (2002).
   PubMed Web of Science ®Google Scholar
• Liu W , DowlingJP, MurrayWKet al. : Rate of growth in melanomas: characteristics and associations of rapidly growing melanomas.Arch. Dermatol.142(12), 1551–1558 (2006).
   PubMed Web of Science ®Google Scholar
• Tejera-Vaquerizo A , Lopez-NavarroN, Alcaide-MartinA, Herrera-AcostaE, Herrera-CeballosE: Correlation of the growth rate of melanoma with the temporal appearance of metastasis.J. Eur. Acad. Dermatol. Venereol.25(3), 366–337 (2011).
   PubMed Web of Science ®Google Scholar
• Bockmann B , GrillHJ, GiesingM: Molecular characterization of minimal residual cancer cells in patients with solid tumors.Biomol. Eng.17(3), 95–111 (2001).
   PubMedGoogle Scholar
• Neagu M , ConstantinC, MandaG, MargaritescuI: Biomarkers of metastatic melanoma.Biomark. Med.3(1), 71–89 (2009).
   PubMed Web of Science ®Google Scholar
• Salti GI , KansagraA, WarsoMA, RonanSG, Das Gupta TK: Clinical node-negative thick melanoma. Arch. Surg.137(3), 291–295 (2002).
   PubMedGoogle Scholar
• Cascinelli N , ClementeC, BifulcoCet al. : Do patients with tumor-positive sentinel nodes constitute a homogeneous group?Ann. Surg. Oncol.8(Suppl. 9), 35S–37S (2001).
   PubMedGoogle Scholar
• Cohn-Cedermark G , Mansson-BrahmeE, RutqvistLE, LarssonO, SingnomklaoT, RingborgU: Metastatic patterns, clinical outcome, and malignant phenotype in malignant cutaneous melanoma.Acta Oncol.38(5), 549–557 (1999).
   PubMed Web of Science ®Google Scholar
• Tejera-Vaquerizo A , Barrera-VigoMV, Fernandez-CanedoIet al. : [Longitudinal study of different metastatic patterns in the progression of cutaneous melanoma].Actas Dermosifiliogr.98(8), 531–538 (2007).
   PubMedGoogle Scholar
• Gershenwald JE , ThompsonW, MansfieldPFet al. : Multi-institutional melanoma lymphatic mapping experience: the prognostic value of sentinel lymph node status in 612 stage I or II melanoma patients.J. Clin. Oncol.17(3), 976–983 (1999).
   PubMed Web of Science ®Google Scholar
• Cascinelli N , BombardieriE, BufalinoRet al. : Sentinel and nonsentinel node status in stage IB and II melanoma patients: two-step prognostic indicators of survival.J. Clin. Oncol.24(27), 4464–4471 (2006).
   PubMed Web of Science ®Google Scholar
• Ross MI , ThompsonJF, GershenwaldJE: Sentinel lymph node biopsy for melanoma: critical assessment at its twentieth anniversary.Surg. Oncol. Clin. N. Am.20(1), 57–78 (2011).
   PubMed Web of Science ®Google Scholar
• Rhodes AR : Prognostic usefulness of sentinel lymph node biopsy for patients who have clinically node negative, localized, primary invasive cutaneous melanoma: a Bayesian analysis using informative published reports.Arch. Dermatol.147(4), 408–415 (2011).
   PubMedGoogle Scholar
• Sartore L , PapanikolaouGE, BiancariF, MazzoleniF: Prognostic factors of cutaneous melanoma in relation to metastasis at the sentinel lymph node.Int. J. Surg.6(3), 205–209 (2008).
   PubMedGoogle Scholar
• Wong SL , KattanMW, McmastersKM, CoitDG: A nomogram that predicts the presence of sentinel node metastasis in melanoma with better discrimination than the American Joint Committee on Cancer staging system.Ann. Surg. Oncol.12(4), 282–288 (2005).
   PubMed Web of Science ®Google Scholar
• Niakosari F , KahnHJ, MccreadyDet al. : Lymphatic invasion identified by monoclonal antibody D2–40, younger age, and ulceration: predictors of sentinel lymph node involvement in primary cutaneous melanoma.Arch. Dermatol.144(4), 462–467 (2008).
   PubMedGoogle Scholar
• Massi D , PuigS, FranchiAet al. : Tumour lymphangiogenesis is a possible predictor of sentinel lymph node status in cutaneous melanoma: a case-control study.J. Clin. Pathol.59(2), 166–173 (2006).
   PubMed Web of Science ®Google Scholar
• Rangel J , NosratiM, TorabianSet al. : Osteopontin as a molecular prognostic marker for melanoma.Cancer112(1), 144–150 (2008).
   PubMed Web of Science ®Google Scholar
• Mraz-Gernhard S , SagebielRW, Kashani-SabetM, MillerJR 3rd, Leong SP: Prediction of sentinel lymph node micrometastasis by histological features in primary cutaneous malignant melanoma. Arch. Dermatol.134(8), 983–987 (1998).
   PubMedGoogle Scholar
• Taylor RC , PatelA, PanageasKS, BusamKJ, BradyMS: Tumor-infiltrating lymphocytes predict sentinel lymph node positivity in patients with cutaneous melanoma.J. Clin. Oncol.25(7), 869–875 (2007).
   PubMed Web of Science ®Google Scholar
• Riber-Hansen R , NyengaardJR, Hamilton-DutoitSJ, SteinicheT: The nodal location of metastases in melanoma sentinel lymph nodes.Am. J. Surg. Pathol.33(10), 1522–1528 (2009).
   PubMed Web of Science ®Google Scholar
• Riber-Hansen R , NyengaardJR, Hamilton-DutoitSJ, SteinicheT: Stage migration after minor changes in histologic estimation of tumor burden in sentinel lymph nodes: the protocol trap.Cancer115(10), 2177–2187 (2009).
   PubMed Web of Science ®Google Scholar
• Murali R , ThompsonJF, ScolyerRA: Location of melanoma metastases in sentinel lymph nodes: what are the implications for histologic processing of sentinel lymph nodes in routine practice?Am. J. Surg. Pathol.34(1), 127–129; author reply 129–131 (2010).
   PubMed Web of Science ®Google Scholar
• Shivers SC , WangX, LiWet al. : Molecular staging of malignant melanoma: correlation with clinical outcome.JAMA280(16), 1410–1415 (1998).
   PubMed Web of Science ®Google Scholar
• Wang X , HellerR, VanvoorhisNet al. : Detection of submicroscopic lymph node metastases with polymerase chain reaction in patients with malignant melanoma.Ann. Surg.220(6), 768–774 (1994).
   PubMed Web of Science ®Google Scholar
• Kammula US , GhosseinR, BhattacharyaS, CoitDG: Serial follow-up and the prognostic significance of reverse transcriptase-polymerase chain reaction – staged sentinel lymph nodes from melanoma patients.J. Clin. Oncol.22(19), 3989–3996 (2004).
   PubMed Web of Science ®Google Scholar
• Scoggins CR , RossMI, ReintgenDSet al. : Prospective multi-institutional study of reverse transcriptase polymerase chain reaction for molecular staging of melanoma.J. Clin. Oncol.24(18), 2849–2857 (2006).
   PubMed Web of Science ®Google Scholar
• Giuliano AE , HuntKK, BallmanKVet al. : Axillary dissection vs no axillary dissection in women with invasive breast cancer and sentinel node metastasis: a randomized clinical trial.JAMA305(6), 569–575 (2011).
   PubMed Web of Science ®Google Scholar
• Morton DL , ThompsonJF, CochranAJet al. : Sentinel-node biopsy or nodal observation in melanoma.N. Engl. J. Med.355(13), 1307–1317 (2006).
   PubMed Web of Science ®Google Scholar
• Kunte C , GeimerT, BaumertJet al. : Analysis of predictive factors for the outcome of complete lymph node dissection in melanoma patients with metastatic sentinel lymph nodes.J. Am. Acad. Dermatol.64(4), 655–662 (2011).
   PubMed Web of Science ®Google Scholar
• Wilson JP , MattsonD, EdgeSB: Is there a need for axillary dissection in breast cancer?J. Natl Compr. Canc. Netw.9(2), 225–230 (2011).
   PubMed Web of Science ®Google Scholar
• Viros A , FridlyandJ, BauerJet al. : Improving melanoma classification by integrating genetic and morphologic features.PLoS Med.5(6), e120 (2008).
   PubMed Web of Science ®Google Scholar
• Broekaert SM , RoyR, OkamotoIet al. : Genetic and morphologic features for melanoma classification.Pigment Cell Melanoma Res.23(6), 763–770 (2010).
   PubMed Web of Science ®Google Scholar
• Long GV , MenziesAM, NagrialAMet al. : Prognostic and clinicopathologic associations of oncogenic BRAF in metastatic melanoma.J. Clin. Oncol.29(10), 1239–1246 (2011).
   PubMed Web of Science ®Google Scholar
• Carlson JA , RossJ, MurphyM: Markers of high-risk cutaneous melanoma: is there a winning combination for individualized prognosis?J. Cutan. Pathol.32(10), 700–703 (2005).
   PubMed Web of Science ®Google Scholar
• Gould Rothberg BE , BergerAJ, MolinaroAMet al. : Melanoma prognostic model using tissue microarrays and genetic algorithms.J. Clin. Oncol.27(34), 5772–5780 (2009).
   PubMed Web of Science ®Google Scholar
• Mcshane LM , AltmanDG, SauerbreiW, TaubeSE, GionM, ClarkGM: REporting recommendations for tumor MARKer prognostic studies (REMARK).Nat. Clin. Pract. Urol.2(8), 416–422 (2005).
   PubMedGoogle Scholar
• Bedin V , AdamRL, De Sa BC, Landman G, Metze K: Fractal dimension of chromatin is an independent prognostic factor for survival in melanoma. BMC Cancer10(1), 260 (2010).
   PubMedGoogle Scholar
• Healy E , BelgaidC, TakataMet al. : Prognostic significance of allelic losses in primary melanoma.Oncogene16(17), 2213–2218 (1998).
   PubMed Web of Science ®Google Scholar
• Daniotti M , OggionniM, RanzaniTet al. : BRAF alterations are associated with complex mutational profiles in malignant melanoma.Oncogene23(35), 5968–5977 (2004).
   PubMed Web of Science ®Google Scholar
• Krouse RS , AlbertsDS, PrasadARet al. : Progression of skin lesions from normal skin to squamous cell carcinoma.Anal. Quant. Cytol. Histol.31(1), 17–25 (2009).
   PubMedGoogle Scholar
• Cremer T , CremerC: Chromosome territories, nuclear architecture and gene regulation in mammalian cells.Nat. Rev. Genet.2(4), 292–301 (2001).
   PubMed Web of Science ®Google Scholar
• Balch CM , GershenwaldJE, SoongSJet al. : Multivariate analysis of prognostic factors among 2,313 patients with stage III melanoma: comparison of nodal micrometastases versus macrometastases.J. Clin. Oncol.28(14), 2452–2459 (2010).
   PubMed Web of Science ®Google Scholar
• Leiter U , MeierF, SchittekB, GarbeC: The natural course of cutaneous melanoma.J. Surg. Oncol.86(4), 172–178 (2004).
   PubMed Web of Science ®Google Scholar
• Pawlik TM , RossMI, ThompsonJF, EggermontAM, GershenwaldJE: The risk of in-transit melanoma metastasis depends on tumor biology and not the surgical approach to regional lymph nodes.J. Clin. Oncol.23(21), 4588–4590 (2005).
   PubMedGoogle Scholar
• Bedikian AY , JohnsonMM, WarnekeCLet al. : Prognostic factors that determine the long-term survival of patients with unresectable metastatic melanoma.Cancer Invest.26(6), 624–633 (2008).
   PubMed Web of Science ®Google Scholar
• Barth A , WanekLA, MortonDL: Prognostic factors in 1,521 melanoma patients with distant metastases.J. Am. Coll. Surg.181(3), 193–201 (1995).
   PubMed Web of Science ®Google Scholar
• Staudt M , LasithiotakisK, LeiterUet al. : Determinants of survival in patients with brain metastases from cutaneous melanoma.Br. J. Cancer102(8), 1213–1218 (2010).
   PubMed Web of Science ®Google Scholar
• Lee ML , TomsuK, Von Eschen KB: Duration of survival for disseminated malignant melanoma: results of a meta-analysis. Melanoma Res.10(1), 81–92 (2000).
   PubMed Web of Science ®Google Scholar
• Dummer R , GarbeC, ThompsonJAet al. : Randomized dose-escalation study evaluating peginterferon α-2a in patients with metastatic malignant melanoma.J. Clin. Oncol.24(7), 1188–1194 (2006).
   PubMed Web of Science ®Google Scholar
• Weinstein IB : Cancer. Addiction to oncogenes – the Achilles heal of cancer.Science297(5578), 63–64 (2002).
   PubMed Web of Science ®Google Scholar
• Brown E , LewisPH, NoceraJ: In search of the silver bullet.Fortune143(10), 166–170, 172, 174 passim (2001).
   PubMedGoogle Scholar
• Lemonick MD , ParkA: New hope for cancer.Time157(21), 62–69 (2001).
   Google Scholar
• Miller AJ , MihmMC Jr: Melanoma. N. Engl. J. Med.355(1), 51–65 (2006).
   PubMed Web of Science ®Google Scholar
• Kalinsky K , HaluskaFG: Novel inhibitors in the treatment of metastatic melanoma.Expert Rev. Anticancer Ther.7(5), 715–724 (2007).
   PubMed Web of Science ®Google Scholar
• Lejeune FJ , RimoldiD, SpeiserD: New approaches in metastatic melanoma: biological and molecular targeted therapies.Expert Rev. Anticancer Ther.7(5), 701–713 (2007).
   PubMed Web of Science ®Google Scholar
• Davies H , BignellGR, CoxCet al. : Mutations of the BRAF gene in human cancer.Nature417(6892), 949–954 (2002).
   PubMed Web of Science ®Google Scholar
• Hocker T , TsaoH: Ultraviolet radiation and melanoma: a systematic review and analysis of reported sequence variants.Hum. Mutat.28(6), 578–588 (2007).
   PubMed Web of Science ®Google Scholar
• Garnett MJ , RanaS, PatersonH, BarfordD, MaraisR: Wild-type and mutant B-RAF activate C-RAF through distinct mechanisms involving heterodimerization.Mol. Cell20(6), 963–969 (2005).
   PubMed Web of Science ®Google Scholar
• Hauschild A , AgarwalaSS, TrefzerUet al. : Results of a Phase III, randomized, placebo-controlled study of sorafenib in combination with carboplatin and paclitaxel as second-line treatment in patients with unresectable stage III or stage IV melanoma.J. Clin. Oncol.27(17), 2823–2830 (2009).
   PubMed Web of Science ®Google Scholar
• Flaherty KT , PuzanovI, KimKBet al. : Inhibition of mutated, activated BRAF in metastatic melanoma.N. Engl. J. Med.363(9), 809–819 (2010).
   PubMed Web of Science ®Google Scholar
• Nazarian R , ShiH, WangQet al. : Melanomas acquire resistance to B-RAF(V600E) inhibition by RTK or N-RAS upregulation.Nature468(7326), 973–977 (2010).
   PubMed Web of Science ®Google Scholar
• Johannessen CM , BoehmJS, KimSYet al. : COT drives resistance to RAF inhibition through MAP kinase pathway reactivation.Nature468(7326), 968–972 (2010).
   PubMed Web of Science ®Google Scholar
• Corcoran RB , Dias-SantagataD, BergethonK, IafrateAJ, SettlemanJ, EngelmanJA: BRAF gene amplification can promote acquired resistance to MEK inhibitors in cancer cells harboring the BRAF V600E mutation.Sci. Signal3(149), ra84 (2010).
   PubMed Web of Science ®Google Scholar
• Villanueva J , VulturA, LeeJTet al. : Acquired resistance to BRAF inhibitors mediated by a RAF kinase switch in melanoma can be overcome by cotargeting MEK and IGF-1R/PI3K.Cancer Cell18(6), 683–695 (2010).
   PubMed Web of Science ®Google Scholar
• Hatzivassiliou G , SongK, YenIet al. : RAF inhibitors prime wild-type RAF to activate the MAPK pathway and enhance growth.Nature464(7287), 431–435 (2010).
   PubMed Web of Science ®Google Scholar
• Poulikakos PI , ZhangC, BollagG, ShokatKM, RosenN: RAF inhibitors transactivate RAF dimers and ERK signalling in cells with wild-type BRAF.Nature464(7287), 427–430 (2010).
   PubMed Web of Science ®Google Scholar
• Omholt K , PlatzA, KanterL, RingborgU, HanssonJ: NRAS and BRAF mutations arise early during melanoma pathogenesis and are preserved throughout tumor progression.Clin. Cancer Res.9(17), 6483–6488 (2003).
   PubMed Web of Science ®Google Scholar
• Edlundh-Rose E , EgyhaziS, OmholtKet al. : NRAS and BRAF mutations in melanoma tumours in relation to clinical characteristics: a study based on mutation screening by pyrosequencing.Melanoma Res.16(6), 471–478 (2006).
   PubMed Web of Science ®Google Scholar
• Martorell-Calatayud A , RequenaC, Botella-EstradaR, SanguezaOP: [Advances in molecular biology and their application in the diagnosis and treatment of melanoma].Actas Dermosifiliogr.100(Suppl. 1), 52–65 (2009).
   PubMedGoogle Scholar
• Greene VR , JohnsonMM, GrimmEA, EllerhorstJA: Frequencies of NRAS and BRAF mutations increase from the radial to the vertical growth phase in cutaneous melanoma.J. Invest. Dermatol.129(6), 1483–1488 (2009).
   PubMed Web of Science ®Google Scholar
• Konstantinopoulos PA , KaramouzisMV, PapavassiliouAG: Post-translational modifications and regulation of the RAS superfamily of GTPases as anticancer targets.Nat. Rev. Drug Discov.6(7), 541–555 (2007).
   PubMed Web of Science ®Google Scholar
• Zhang FL , KirschmeierP, CarrDet al. : Characterization of Ha-ras, N-ras, Ki-Ras4A, and Ki-Ras4B as in vitro substrates for farnesyl protein transferase and geranylgeranyl protein transferase type I.J. Biol. Chem.272(15), 10232–10239 (1997).
   PubMed Web of Science ®Google Scholar
• Vivanco I , SawyersCL: The phosphatidylinositol 3-Kinase AKT pathway in human cancer.Nat. Rev. Cancer2(7), 489–501 (2002).
   PubMed Web of Science ®Google Scholar
• Mirmohammadsadegh A , MariniA, NambiarSet al. : Epigenetic silencing of the PTEN gene in melanoma.Cancer Res.66(13), 6546–6552 (2006).
   PubMed Web of Science ®Google Scholar
• Wu H , GoelV, HaluskaFG: PTEN signaling pathways in melanoma.Oncogene22(20), 3113–3122 (2003).
   PubMed Web of Science ®Google Scholar
• Goel VK , LazarAJ, WarnekeCL, RedstonMS, HaluskaFG: Examination of mutations in BRAF, NRAS, and PTEN in primary cutaneous melanoma.J. Invest. Dermatol.126(1), 154–160 (2006).
   PubMed Web of Science ®Google Scholar
• Courtney KD , CorcoranRB, EngelmanJA: The PI3K pathway as drug target in human cancer.J. Clin. Oncol.28(6), 1075–1083 (2010).
   PubMed Web of Science ®Google Scholar
• Margolin K , LongmateJ, BarattaTet al. : CCI-779 in metastatic melanoma: a phase II trial of the California Cancer Consortium.Cancer104(5), 1045–1048 (2005).
   PubMed Web of Science ®Google Scholar
• Chresta CM , DaviesBR, HicksonIet al. : AZD8055 is a potent, selective, and orally bioavailable ATP-competitive mammalian target of rapamycin kinase inhibitor with in vitro and in vivo antitumor activity.Cancer Res.70(1), 288–298 (2010).
   PubMed Web of Science ®Google Scholar
• Jaiswal BS , JanakiramanV, KljavinNMet al. : Combined targeting of BRAF and CRAF or BRAF and PI3K effector pathways is required for efficacy in NRAS mutant tumors.PLoS One4(5), E5717 (2009).
   PubMed Web of Science ®Google Scholar
• Beadling C , Jacobson-DunlopE, HodiFSet al. : KIT gene mutations and copy number in melanoma subtypes.Clin. Cancer Res.14(21), 6821–6828 (2008).
   PubMed Web of Science ®Google Scholar
• Woodman SE , DaviesMA: Targeting KIT in melanoma: a paradigm of molecular medicine and targeted therapeutics.Biochem. Pharmacol.80(5), 568–574 (2010).
   PubMed Web of Science ®Google Scholar
• Hodi FS , FriedlanderP, CorlessCLet al. : Major response to imatinib mesylate in KIT-mutated melanoma.J. Clin. Oncol.26(12), 2046–2051 (2008).
   PubMed Web of Science ®Google Scholar
• Woodman SE , TrentJC, Stemke-HaleKet al. : Activity of dasatinib against L576P KIT mutant melanoma: molecular, cellular, and clinical correlates.Mol. Cancer Ther.8(8), 2079–2085 (2009).
   PubMed Web of Science ®Google Scholar
• Quintas-Cardama A , LazarAJ, WoodmanSE, KimK, RossM, HwuP: Complete response of stage IV anal mucosal melanoma expressing KIT Val560Asp to the multikinase inhibitor sorafenib.Nat. Clin. Pract. Oncol.5(12), 737–740 (2008).
   PubMedGoogle Scholar
• Kluger HM , DudekAZ, MccannCet al. : A Phase 2 trial of dasatinib in advanced melanoma.Cancer117(10), 2202–2208 (2011).
   PubMed Web of Science ®Google Scholar
• Van Raamsdonk CD , BezrookoveV, GreenGet al. : Frequent somatic mutations of GNAQ in uveal melanoma and blue naevi.Nature457(7229), 599–602 (2009).
   PubMed Web of Science ®Google Scholar
• Onken MD , WorleyLA, LongMDet al. : Oncogenic mutations in GNAQ occur early in uveal melanoma.Invest. Ophthalmol. Vis. Sci.49(12), 5230–5234 (2008).
   PubMed Web of Science ®Google Scholar
• Van Raamsdonk CD , GriewankKG, CrosbyMBet al. : Mutations in GNA11 in uveal melanoma.N. Engl. J. Med.363(23), 2191–2199 (2010).
   PubMed Web of Science ®Google Scholar
• Downey SG , KlapperJA, SmithFOet al. : Prognostic factors related to clinical response in patients with metastatic melanoma treated by CTL-associated antigen-4 blockade.Clin. Cancer Res.13(22 Pt 1), 6681–6688 (2007).
   PubMed Web of Science ®Google Scholar
• Weber JS , O‘dayS, UrbaWet al. : Phase I/II study of ipilimumab for patients with metastatic melanoma.J. Clin. Oncol.26(36), 5950–5956 (2008).
   PubMed Web of Science ®Google Scholar
• Beck KE , BlansfieldJA, TranKQet al. : Enterocolitis in patients with cancer after antibody blockade of cytotoxic T-lymphocyte-associated antigen 4.J. Clin. Oncol.24(15), 2283–2289 (2006).
   PubMed Web of Science ®Google Scholar
• Peggs KS , QuezadaSA: Ipilimumab: attenuation of an inhibitory immune checkpoint improves survival in metastatic melanoma.Expert Rev. Anticancer Ther.10(11), 1697–1701 (2010).
   PubMed Web of Science ®Google Scholar
• Hodi FS , O‘daySJ, McdermottDFet al. : Improved survival with ipilimumab in patients with metastatic melanoma.N. Engl. J. Med.363(8), 711–723 (2010).
   PubMed Web of Science ®Google Scholar
• Mcdermott DF , SosmanJA, GonzalezRet al. : Double-blind randomized Phase II study of the combination of sorafenib and dacarbazine in patients with advanced melanoma: a report from the 11715 Study Group.J. Clin. Oncol.26(13), 2178–2185 (2008).
   PubMed Web of Science ®Google Scholar
• Camacho LH , AntoniaS, SosmanJet al. : Phase I/II trial of tremelimumab in patients with metastatic melanoma.J. Clin. Oncol.27(7), 1075–1081 (2009).
   PubMed Web of Science ®Google Scholar
• Brahmer JR , DrakeCG, WollnerIet al. : Phase I study of single-agent anti-programmed death-1 (MDX-1106) in refractory solid tumors: safety, clinical activity, pharmacodynamics, and immunologic correlates.J. Clin. Oncol.28(19), 3167–3175 (2010).
   PubMed Web of Science ®Google Scholar
• Winfield HL , KirklandF, Ramos-CeballosFI, HornTD: Osteopontin expression in spitz nevi.Arch. Dermatol.143(8), 1076–1077 (2007).
   PubMedGoogle Scholar
• Svobodova S , BrowningJ, MacgregorDet al. : Cancer-testis antigen expression in primary cutaneous melanoma has independent prognostic value comparable to that of Breslow thickness, ulceration and mitotic rate.Eur. J. Cancer47(3), 460–469 (2011).
   PubMed Web of Science ®Google Scholar

▪ Websites

• Ries L , MelbertD, KrapchoMet al.: SEER Cancer Statistics Review, 1975–2004http://seer.cancer.gov/csr/1975_2004/
   Google Scholar
• Australian Institute of Health and Welfare (AIHW) : ACIM Books.AIHW (2010) www.aihw.gov.au/acim-books
   Google Scholar