Adrenocortical Carcinoma (eBook)
XV, 546 Seiten
Springer New York (Verlag)
978-0-387-77236-3 (ISBN)
We anticipate the book to be a definitive text on the subject that explores all aspects of the study of adrenal cancer and the treatment of patients with the disease. Chapters will cover epidemiology, pathogenesis, genetics, cancer stem cells, historic and emerging therapies, mouse models of adrenal cancer, new developments in tumor profiling, worldwide collaborative groups and tumor registries together with resources for the practitioner and community of adrenal cancer scientists.
We do not wish this book to compete with the other larger books in the Endocrine and Endocrine Surgery literature. In addition, it is not expected to cover benign adrenal diseases that have been covered in detail in other venues. We envision this book to be a very specialized and exhaustive text on basic, translational and clinical aspects of adrenal cancer.
We anticipate the book to be a definitive text on the subject that explores all aspects of the study of adrenal cancer and the treatment of patients with the disease. Chapters will cover epidemiology, pathogenesis, genetics, cancer stem cells, historic and emerging therapies, mouse models of adrenal cancer, new developments in tumor profiling, worldwide collaborative groups and tumor registries together with resources for the practitioner and community of adrenal cancer scientists.We do not wish this book to compete with the other larger books in the Endocrine and Endocrine Surgery literature. In addition, it is not expected to cover benign adrenal diseases that have been covered in detail in other venues. We envision this book to be a very specialized and exhaustive text on basic, translational and clinical aspects of adrenal cancer.
Preface 5
Contents 7
Contributors 10
Part I History of Adrenocortical Carcinoma Research and Clinical Care 15
1 The History of Adrenocortical Carcinoma Treatment A Medical Perspective 16
References 21
2 The History of Adrenocortical Carcinoma Treatment A Surgical Perspective 22
References 31
Part II Epidemiology, Presentation and Diagnosis 33
3 Epidemiology of Adrenocortical Carcinoma 34
3.1 Incidence of Adrenocortical Carcinoma 34
3.2 Risk Factors for Adrenocortical Carcinoma 35
3.3 Stage at Presentation 36
3.4 Prognosis of Adrenocortical Carcinoma 37
3.5 Associated Malignancies 38
References 38
4 Clinical Presentation and Initial Diagnosis 41
4.1 Clinical Presentation 41
4.1.1 Hormone Excess 41
4.1.2 Loco-Regional Manifestations 44
4.1.3 Unspecific Symptoms -- Metastatic Disease 45
4.1.4 Incidentally Detected Adrenocortical Carcinoma 46
4.2 Laboratory Work-Up 46
4.3 Imaging at Presentation 49
4.4 Fine-Needle Aspiration/Cut Biopsy 51
References 53
5 Diagnostic Approach to Incidentaloma 58
5.1 Does the Adrenal Lesion Exhibit a Biologically Benign or Malignant Behavior? 59
5.1.1 Evidence from Epidemiological Studies -- Adrenocortical Tumors 59
5.1.2 Evidence from Epidemiological Studies -- Pheochromocytomas 60
5.1.3 Evidence from Epidemiological Studies -- Metastasis 60
5.1.4 Evidence from Epidemiological Studies -- Other Adrenal Lesions 61
5.1.5 Evidence from Imaging Studies 61
5.1.6 Evidence from Biopsy Studies 62
5.2 Is the Adrenal Lesion a Source of Autonomous Hormone Hypersecretion? 63
5.2.1 Evidence from Epidemiological Studies 63
5.2.2 Hormone Excess 64
5.2.2.1 Hypercortisolism 64
5.2.2.2 Hyperaldosteronism 65
5.2.2.3 Pheochromocytoma 66
5.2.2.4 Hyperandrogenemia 66
5.2.2.5 Other Endocrine Functions 66
5.3 Is Surgical Removal Necessary or Is an Observational Policy a Safe and Reasonable Approach? 67
References 68
Part III Imaging 74
6 Computed Tomography/Magnetic Resonance Imaging of Adrenocortical Carcinoma 75
6.1 Clinical Utility of CT and MRI 77
6.2 Pheochromocytoma 78
6.3 The Incidentally Discovered Adrenal Mass (Incidentaloma) 78
6.4 Myelolipoma 79
6.5 Cyst 80
6.6 Hemorrhage 80
6.7 Adrenocortical Adenoma 81
6.8 Adrenocortical Carcinoma 82
6.9 Metastasis 84
6.10 Differential Diagnosis: Adrenocortical Adenoma or Metastasis? 85
6.11 Differential Diagnosis: Adrenocortical Adenoma or Carcinoma? 89
6.12 Imaging and Staging of Adrenocortical Carcinoma 90
References 90
7 Functional Imaging of Adrenocortical Carcinoma 93
7.1 [18F]-FDG-PET-CT in Adrenocortical Carcinoma 93
7.2 Molecular Imaging with Specific Adrenocortical Tracers 97
7.2.1 Norcholesterol Scintigraphy 98
7.2.2 Enzyme Inhibitors 100
7.2.3 Metomidate 100
7.2.4 [18F]-Fluoro-etomidate 104
7.2.5 [123I /131I]-Iodo-metomidate 104
References 106
Part IV Pathology 112
8 Classical Histopathology and Immunohistochemistry 113
8.1 Gross Findings 113
8.2 Histopathology 115
8.3 Scoring Systems 118
8.4 Immunocytochemistry 122
8.5 Ultrastructure 124
8.6 Grading 125
8.7 Staging 126
8.8 Differential Diagnosis 127
References 129
9 Cellular and Molecular Pathology of Adrenocortical Carcinoma 133
9.1 Clonality 134
9.2 Genomic and Genetic Abnormalities 135
9.2.1 Ploidy and DNA Content of Adrenocortical Tumors 135
9.2.2 Genomic Aberrations in Adrenocortical Carcinoma: Analysis by Comparative Genomic Hybridization (CGH) 136
9.2.3 LOH and Mutation Analysis of Genomic Loci and Genes 138
9.3 The RAS-Associated Signaling Networks in Adrenocortical Carcinoma 143
9.4 Angiogenesis in Adrenocortical Carcinoma 145
9.5 Peptide Hormones and Cytokines in Adrenocortical Carcinoma 146
9.6 Contributions of Physiological Regulators of the HPA-Axis, ACTH, and Steroid Hormones to Adrenocortical Tumorigenesis 148
9.7 Timing of the Occurrence of Tumorigenesis-Related Changes 149
References 151
Part V Genetic and Molecular Aspects 157
10 Overview of Genetic Syndromes Associated with Adrenocortical Cancer 158
10.1 Syndromes Associated with Adrenocortical Cancer 165
10.1.1 The Overgrowth Syndromes: BWS and IHH 165
10.1.2 Li--Fraumeni Syndrome 169
10.1.3 Familial Adenomatous Polyposis 169
10.1.4 Multiple Endocrine Neoplasia Type 1 170
10.1.5 Neurofibromatosis Type 1 172
10.2 Screening for Germline Mutations in Adrenocortical Cancer Patients 172
10.3 Screening and Surveillance of Patients with Hereditary Syndromes Predisposing to Adrenocortical Cancer 173
References 174
11 Li-Fraumeni Syndrome 178
11.1 Clinical Definition of LFS 178
11.2 Cancer Risk Patterns in LFS Families 180
11.3 The TP53 Tumor Suppressor 180
11.4 TP53 Gene Inactivation 182
11.5 TP53 and the LFS 183
11.6 The Role of Other Genes in LFS 184
11.7 Modifier Genes in LFS 184
11.8 The Unique Brazilian LFS-TP53Codon 337 Mutation Phenotype 185
11.9 Functional Models of Germline TP53 Mutations 186
11.10 Mouse Models of LFS 187
11.11 Medical and Ethical Considerations 190
References 192
12 TP53 Molecular Genetics 197
12.1 The Pre-eminent Tumor Suppressor 197
12.2 Transcription Is Key 198
12.3 The TP53 Signaling Pathway: Loops Within Loops 199
12.4 Acquired and Inherited TP53 Mutations 201
12.5 TP53 Mutations in Childhood and Adult Adrenocortical Tumors 201
12.6 Low-Penetrance Mutant TP53 Alleles 202
12.7 Genetic Modifiers 204
12.8 Concluding Thoughts 205
References 206
13 Telomeres and Telomerase in Adrenocortical Carcinoma 210
13.1 The End-Replication Problem and Telomerase 211
13.2 Telomeres 213
13.3 Telomere-Based Model of Carcinogenesis 216
13.4 Telomerase in Experimental Adrenocortical Carcinoma 218
13.5 Human Syndromes with Defects in Telomere Physiology 220
13.6 Telomerase and Adrenocortical Carcinoma 221
13.7 Telomeres and Adrenocortical Carcinoma 221
References 224
14 Beckwith--Wiedemann Syndrome 229
14.1 Diagnosis 229
14.2 Clinical Features 230
14.3 Genetics 232
14.4 Cancer 233
References 235
15 The Insulin-Like Growth Factor System in Adrenocortical Growth Control and Carcinogenesis 237
15.1 The IGF System 237
15.2 The Role of the IGF System in the Normal Adult Adrenal Gland 238
15.2.1 Insulin-Like Growth Factors 238
15.2.2 IGF Receptors 240
15.2.3 IGF-Binding Proteins 240
15.3 Specific Role of the IGF System in Adrenocortical Tumorigenesis 242
15.3.1 IGF1 242
15.3.2 IGF2 245
15.4 IGF Receptors 249
15.4.1 The IGF1R 249
15.4.2 The IGF2/Mannose-6-Phosphate (IGF2R)-Receptor 251
15.5 IGFBPs 252
15.6 Summary and Conclusion 255
References 257
16 WNT/-Catenin Signaling in Adrenocortical Carcinoma 265
16.1 The WNT/-Catenin Signaling Pathway 266
16.1.1 Molecular Mechanisms of the Canonical WNT/-Catenin Signaling Pathway 266
16.1.2 Components of the WNT/-Catenin Signaling Pathway 267
16.1.2.1 Initiation of the WNT/-Catenin Signaling Pathway at the Cell Membrane 267
16.1.2.2 WNT/-Catenin Signaling Events in the Cytoplasm 268
16.1.2.3 Nuclear Components of the WNT/-Catenin Signaling Pathway 270
16.1.3 The WNT/-Catenin Signaling Pathway Target Genes 271
16.2 The WNT/-Catenin Signaling Pathway in Familial Adenomatous Polyposis Coli 271
16.3 The WNT/-Catenin Signaling Pathway in the Adrenal Cortex and in Adrenocortical Tumors 271
16.3.1 Adrenal Cortex Development 271
16.3.2 Adrenocortical Diseases 272
16.4 The WNT Signaling Pathway in Adrenocortical Carcinoma 276
16.4.1 Activation of the WNT/ -Catenin Pathway and -Catenin Mutations 276
16.4.2 Role of -Catenin Activation in Adrenocortical Tumor Development 276
16.4.3 Alternatives to CTNNB1 Mutation for WNT/-Catenin Pathway Activation in Adrenocortical Carcinoma 277
16.4.3.1 WTX, AXIN1, AXIN2, or GSK3 278
16.4.3.2 APC 278
16.5 The WNT/-Catenin Signaling Pathway: A Potential Target for Cancer Treatment 278
16.6 Conclusion 279
References 279
Part VI Models of Adrenocortical Cancer 285
17 Adrenocortical Stem and Progenitor Cells: Implications for Cancer 286
17.1 Adrenocortical Tumors 288
17.2 Normal Adrenal Adult Stem Cells 289
17.2.1 Adrenal Development and Structure 289
17.2.2 Where Do the Adrenal Adult Stem Cells Reside? 290
17.2.3 Establishment of the Stem Cell Niche 291
17.2.3.1 Adrenal Precursor Cells in Fetal Zone 292
17.2.3.2 Stem/Progenitor Cells in Adrenal Capsule 292
17.3 What Factors Regulate Adrenal Adult Stem and Progenitor Cells? 294
17.3.1 Dax1 294
17.3.2 Shh 295
17.3.3 Wnt/-Catenin 295
17.3.4 IGF2 296
17.3.5 Telomerase 296
17.4 How Do Normal Adrenal Cells Become Cancer Cells/or How Is Adrenocortical Carcinoma Initiated? 296
17.4.1 Wnt/-Catenin 297
17.4.2 IGF2 298
17.4.3 Pod1 299
17.4.4 p53/Telomerase 299
17.5 How Is Adrenocortical Carcinoma Maintained: Cancer Stem Cell or Stochastic Model? 300
17.6 Summary 301
References 302
18 Adrenocortical Cell Lines 306
18.1 Human Adrenocortical Cell Lines 308
18.1.1 The NCI-H295, NCI-H295R, and NCI-H295A Adrenocortical Carcinoma Cell Lines 308
18.1.1.1 Origin and Development 308
18.1.1.2 Cell Line Growth and Characterization 310
18.1.1.3 Expression of Hormone Receptors and Hormonal Responsiveness 311
18.1.1.4 Steroidogenesis 312
18.1.1.5 Steroidogenic Enzyme Expression 313
18.1.1.6 NCI-H295 Cell Line As Adrenal Cancer Therapy Tool 313
18.1.2 Human Adrenocortical Carcinoma, Clone 15 (HAC15) Cell Line, and Related Clones 314
18.1.3 Pediatric Adrenocortical Adenoma Derived Cell Line 315
18.1.3.1 Origin and Development 315
18.1.3.2 Growth and Steroidogenesis 315
18.1.4 The SW13 Human Adrenal Carcinoma Derived Cell Line 315
18.1.5 The ACT-1 Human Adrenal Carcinoma Derived Cell Line 315
18.1.6 The RL-251 Human Adrenal Carcinoma Derived Cell Line 316
18.1.7 Human Adrenal Cell Lines from Viral Oncogenes 316
18.2 Rodent Adrenocortical Cell Lines 317
18.2.1 The Y1 Adrenal Cell Line 317
18.2.2 Experimentally Induced Rodent Adrenal Cell Lines 318
18.3 Bovine Adrenocortical Cell Lines 319
18.4 Summary 319
References 320
19 Mouse Models of Adrenal Tumorigenesis 326
19.1 Mouse Models with Spontaneous or Induced Adrenal Tumor Growth 327
19.2 Mouse Models Utilizing Transplanted Adrenal Tumor Cells 329
19.3 Genetically Modified Mouse Models with an Adrenal Tumor Phenotype 334
19.4 Mouse Models with Transgenic Expression of an Oncogene-Inducing Adrenal Tumor 334
19.5 Mouse Models with Targeted Deletions Inducing Adrenal Tumors 336
References 337
Part VII Therapies 342
20 Overview of Treatment Options for Adrenocortical Carcinoma 343
20.1 Adjuvant Treatment 344
20.2 Treatment of Metastatic Disease 344
20.3 Medical Treatment of Adrenocortical Carcinoma Steroidogenic Hormone Excess 346
20.4 Emerging Therapies 346
References 347
21 Chemotherapy 350
21.1 Single-Agent Chemotherapy 351
21.2 Combination Chemotherapy 353
21.3 Chemotherapy Plus Mitotane 356
21.4 Chemotherapy Plus Target Therapy 360
21.5 The FIRM-ACT Study 361
21.6 Prognostic and Predictive Factors of Response to Chemotherapy in Advanced Patients 362
21.7 Conclusion 364
References 364
22 Mitotane 368
22.1 Pharmacokinetics 368
22.2 Historical Background 369
22.3 Mitotane in Advanced Adrenocortical Carcinoma 370
22.4 Toxicity and Dosage 372
22.5 Mitotane in Adjuvant Setting 374
References 378
23 Pharmacotherapy for Hormone Excess in AdrenocorticalCarcinoma 381
23.1 Adrenal Steroid Biosynthesis 381
23.1.1 Basics of Adrenal Steroidogenesis and Zonation 381
23.1.2 Steroidogenic Enzymes 383
23.1.3 Steroidogenic Pathways in the Adrenal Gland 385
23.1.4 Acute and Chronic Regulation of Adrenal Steroidogenesis and Dysregulation in Adrenocortical Carcinoma 386
23.2 Approach to the Adrenocortical Carcinoma Patient 387
23.2.1 Clinical Manifestations of Adrenal Steroid Excess 387
23.2.2 Therapeutic Strategies 388
23.3 Specific Treatments 389
23.3.1 Mineralocorticoid Excess 389
23.3.1.1 Inhibitors of Mineralocorticoid Synthesis 389
23.3.1.2 Mineralocorticoid Receptor Antagonists 390
23.3.1.3 Nonspecific Treatment of Hypertension and Hypokalemia 391
23.3.2 Glucocorticoid Excess 391
23.3.2.1 Inhibitors of Glucocorticoid Synthesis 392
23.3.2.2 Glucocorticoid Receptor Antagonists 394
23.3.2.3 Nonspecific Treatment of Cardiovascular and Metabolic Consequences 394
23.3.3 Androgen Excess 394
23.3.3.1 Inhibitors of Androgen Synthesis 395
23.3.3.2 Androgen Receptor Antagonists 395
23.3.3.3 Nonspecific Treatment of Androgen Excess 396
23.3.4 Treatment of Estrogen Excess 396
23.4 Conclusions 397
References 397
24 Surgery for Adrenocortical Carcinoma 401
24.1 Surgical Adrenal Anatomy 402
24.1.1 Arterial Supply 403
24.1.2 Venous Drainage 404
24.1.3 Lymphatics 404
24.1.4 Adjacent Structures 404
24.2 Perioperative Considerations 406
24.2.1 Preoperative 406
24.2.2 Intraoperative 408
24.2.3 Postoperative 409
24.3 Role of Surgery 409
24.3.1 Primary Therapy -- Curative Intent 409
24.3.2 Recurrences 410
24.3.3 Palliation: Hormonal Control and Tumor Debulking 411
24.4 Surgical Approaches to the Adrenal Glands 412
24.4.1 Anterior Transabdominal -- Open 412
24.4.2 Thoracoabdominal 413
24.4.3 Approaches to Difficult Resections 414
24.4.3.1 Vascular Control and Resection 416
24.4.4 Laparoscopic Surgery for Primary Adrenal Malignancy 418
24.5 Surgical Complications 420
24.6 Conclusion 421
References 421
25 Radiation Therapy for Adrenocortical Carcinoma 424
25.1 Current Surgical and Adjuvant Management 425
25.2 Radiotherapy for Adrenocortical Carcinoma 428
25.3 Case Studies 431
25.3.1 Case #1. Adjuvant Radiotherapy 431
25.3.2 Case #2. Adjuvant Radiotherapy After Resection of a Local Recurrence 433
25.3.3 Case #3. Palliation of a Bulky Liver Metastasis 434
25.4 Summary 435
References 435
26 Follow-Up and Monitoring of Adrenocortical Carcinoma 439
26.1 General Modalities for Follow-Up 440
26.2 History 440
26.3 Physical Examination 440
26.4 Laboratory Evaluation 441
26.5 Imaging 442
26.5.1 Symptom-Specific/Sign-Specific Imaging 443
26.5.2 Cross-Sectional Imaging 443
26.5.3 Functional Imaging 444
26.6 Risk-Based Follow-Up Strategies 445
26.6.1 Low-Risk Localized Disease/Complete Resection 446
26.6.2 High-Risk Disease/Complete Resection 446
26.6.3 Unresectable Localized or Metastatic Disease 447
26.7 Risk Modifiers and Follow-Up Strategies 447
26.8 Conclusion 448
References 448
Part VIII Unique Cohorts and Future Perspectives 450
27 Aldosterone-Producing Adrenocortical Carcinoma 451
27.1 Epidemiology 451
27.2 Clinical and Hormonal Features 452
27.3 Pathology 454
27.4 Imaging Characteristics 455
27.5 Prognosis 455
27.6 Treatment 456
References 458
28 Adrenocortical Cancer in Children 460
28.1 Epidemiology of Adrenocortical Cancer 460
28.2 Biology of Adrenocortical Carcinoma 461
28.3 Clinical Characteristics of Pediatric Adrenocortical Carcinoma 464
28.4 Diagnosis of Adrenocortical Carcinoma 465
28.5 Prognostic Factors 466
28.6 Treatment of Pediatric Adrencortical Carcinoma 468
28.7 A Collaborative Research Initiative for Childhood Adrenocortical Carcinoma 470
References 471
29 Genome-Wide Studies in Adrenocortical Neoplasia 475
29.1 Introduction and the Potential of Genomic Studies 475
29.2 Genome-Wide Gene Expression Studies 475
29.3 Array-Based Comparative Genomic Hybridization 480
29.4 MicroRNA Profiling 481
29.5 Molecular Profiling and Its Potential Impact on Adrenal Pathology and Management of Patients with Adrenal Cancer 481
29.5.1 Diagnosis 481
29.5.2 Prognosis 482
29.5.3 Prediction 482
29.6 Conclusion 482
References 482
30 New Strategies for the Treatment of Adrenocortical Carcinoma 484
30.1 Therapy Targeted Towards Altered Signaling Pathways in Adrenocortical Carcinoma Cells 484
30.1.1 Identification of Potential Signaling Targets 484
30.1.1.1 Target Identification from the Study of Genetic Syndromes 485
30.1.1.2 Targets Identified from Gene Expression Analysis 488
30.1.2 Targeting the IGF2-IGF1R Pathway 488
30.1.2.1 Small Molecule TKIs 488
30.1.2.2 Anti-IGF1R Antibodies 489
30.1.3 Targeting the FGF Receptor 489
30.1.4 Targeting the EGF Receptor 490
30.1.5 Multi-kinase Inhibition Strategies 490
30.1.6 Targeting the Wnt Signaling Pathway 490
30.2 Enhancing the Effectiveness of Cytotoxic Chemotherapy 491
30.3 Proapoptoic Strategies 491
30.4 Novel Strategies 492
30.4.1 Targeting Tumor Vasculature 492
30.4.2 Targeting the Microenvironment 494
30.4.2.1 Fibroblasts of the Microenvironment 495
30.4.2.2 Immune Cells of the Microenvironment 496
30.4.2.3 Proteolytic Enzymes in the Microenvironment 496
30.4.3 Therapy Aimed at Metastasis Suppression 497
30.5 Delivery of Newer Modes of Therapy 498
30.6 Summary and Future Directions 499
References 500
Part IX Adrenal Cancer Networks and Registries 505
31 The Dutch Adrenal Network 506
31.1 The Dutch Adrenal Network 506
31.2 The Dutch Adrenal Registry 507
31.3 Results 507
31.4 Future Goals 508
31.5 Conclusion 508
32 The ENS@T Initiative 509
32.1 The History: From National Networks to ENS@T 509
32.2 Increasing the Patient Number 510
32.3 Increasing Technical and Methodological Exchange 511
32.4 The Idea of Exchange 512
32.4.1 Harmonization 512
32.4.2 Material 512
32.4.3 Science 512
32.5 Examples of Research Advancements 513
32.6 Organizing the Network 515
32.6.1 The Steering Committee 515
32.6.2 The Working Groups 515
32.6.3 ENS@T Website 516
32.7 Financing the Network 516
32.8 Perspectives 516
32.8.1 Integrational and Disseminative Effects of a European Network 517
References 518
Index 520
| Erscheint lt. Verlag | 23.11.2010 |
|---|---|
| Zusatzinfo | XV, 546 p. |
| Verlagsort | New York |
| Sprache | englisch |
| Themenwelt | Medizin / Pharmazie ► Medizinische Fachgebiete ► Onkologie |
| Studium ► 1. Studienabschnitt (Vorklinik) ► Biochemie / Molekularbiologie | |
| ISBN-10 | 0-387-77236-7 / 0387772367 |
| ISBN-13 | 978-0-387-77236-3 / 9780387772363 |
| Haben Sie eine Frage zum Produkt? |
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