| Diagnostic and Prognostic Biomarkers and Therapeutic Targets in Melanoma | 3 |
|---|
| Preface | 7 |
| Contents | 9 |
| Contributors | 11 |
| 1: Introduction to Diagnostic and Prognostic Biomarkers and Therapeutic Targets in Melanoma | 15 |
| References | 21 |
| 2: Diagnostic and Prognostic Biomarkers in Melanoma: Current State of Play | 22 |
| Introduction | 22 |
| Tumor Tissue-Based Biomarkers | 22 |
| Serological Markers | 25 |
| Perspective | 27 |
| References | 27 |
| 3: Molecular Pathogenesis of Melanoma: Established and Novel Pathways | 32 |
| Introduction | 32 |
| Molecular Pathways Involved in Melanoma | 33 |
| Established Pathways | 34 |
| RAS/RAF/MEK/ERK Signaling | 34 |
| KIT | 36 |
| High-Risk Melanoma Susceptibility Genes (CDKN2A and CDK4) | 37 |
| Low-Risk Melanoma Susceptibility Genes | 38 |
| PTEN and PI3K-AKT Pathways | 39 |
| MITF | 40 |
| Novel Pathways | 41 |
| Notch1 | 41 |
| Nuclear Factor- k B | 42 |
| iNOS | 43 |
| Conclusion | 44 |
| References | 45 |
| 4: Staging of Melanoma | 51 |
| TNM Classification | 51 |
| T – Primary Tumor | 51 |
| Primary Tumor Thickness | 51 |
| Ulceration | 51 |
| Mitotic Rate | 52 |
| N – Regional Lymph Nodes | 53 |
| Micrometastases Versus Macrometastases | 53 |
| Intralymphatic Metastases | 54 |
| Immunohistochemical (IHC) Detection of Micrometastases | 54 |
| M – Distant Metastasis | 54 |
| Metastatic Melanoma of Unknown Primary Site | 55 |
| Clinical Versus Histopathologic Staging | 55 |
| Clinical Staging | 55 |
| Histopathologic Staging | 56 |
| Stage Groups | 56 |
| Localized Melanoma (Stages I and II) | 56 |
| Regional Metastases (Stage III) | 57 |
| Distant Metastases (Stage IV) | 57 |
| Updates and Changes in the 7th Edition AJCC Melanoma Staging System | 57 |
| Final Comments and Future Applications | 58 |
| References | 59 |
| 5: Clinical and Histopathological Parameters in Melanoma | 61 |
| Introduction | 61 |
| Age | 61 |
| Anatomic Location | 62 |
| Gender | 62 |
| Breslow Thickness | 62 |
| Clark Anatomic Level | 63 |
| Tumor Volume | 64 |
| Cross-Sectional Profile | 64 |
| Ulceration | 65 |
| Mitotic Rate | 65 |
| Radial and Vertical Growth Phases | 66 |
| Regression | 67 |
| Host Inflammatory Response | 68 |
| Tumor Vascularity | 68 |
| Vascular Invasion | 69 |
| Angiotropism | 69 |
| Histological Tumor Type | 69 |
| Cytologic Variants | 70 |
| Desmoplasia | 71 |
| Neurotropic Melanoma | 71 |
| Cytologic Atypia | 71 |
| Borderline Melanocytic Lesions | 72 |
| Association with a Benign Melanocytic Nevus | 72 |
| Paratumoral Epidermal Hyperplasia | 72 |
| Satellite and In-Transit Metastasis | 73 |
| Sentinel Lymph Nodes | 73 |
| Conclusion | 73 |
| References | 75 |
| 6: Genetic/Epigenetic Biomarkers: Distinction of Melanoma from Other Melanocytic Neoplasms | 80 |
| Introduction | 80 |
| Allelic Imbalance (AI) Analysis | 80 |
| Comparative Genomic Hybridization (CGH) | 81 |
| Multiplex Ligation-Dependent Probe Amplification (MLPA) | 82 |
| Fluorescence In Situ Hybridization (FISH) | 82 |
| Analysis of BRAF, NRAS, and HRAS Gene Mutation | 83 |
| Gene Expression Analysis Using DNA Microarrays | 84 |
| Epigenetic Biomarkers | 84 |
| Combination of Mutational Analysis and Methylation-Specific MLPA | 85 |
| Case 1 | 85 |
| Case 2 | 85 |
| Conclusion | 87 |
| References | 87 |
| 7: mRNA Biomarkers in Melanoma | 89 |
| Introduction | 89 |
| Melanomagenesis | 91 |
| Dysplastic Nevi and Melanoma Progression | 92 |
| From RGP Melanoma to VGP Melanoma: The Big Step | 92 |
| From Primary Melanoma to Metastatic Disease | 93 |
| Gene Expression Profiling and Outcome | 95 |
| Conclusion | 97 |
| References | 97 |
| 8: Epigenetic Biomarkers in Melanoma | 99 |
| Introduction | 99 |
| DNA Methylation | 101 |
| Aberrant DNA Hypermethylation | 101 |
| Aberrant DNA Hypomethylation | 104 |
| Clinical Applications | 105 |
| DNA Methylation as Biomarkers in Melanoma | 105 |
| Histone Modifications | 107 |
| Histone Acetylation and Methylation | 108 |
| Clinical Applications | 108 |
| Histone Modifications as Biomarkers in Melanoma | 110 |
| MicroRNAs | 112 |
| Conclusions | 115 |
| References | 115 |
| 9: MicroRNA Biomarkers in Melanoma<
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