Methods of Cancer Diagnosis, Therapy, and Prognosis (eBook)

Contributors 7
Preface 14
Introduction 16
Identification of Biomarkers for Clear Cell Ovarian Adenocarcinoma 47
Introduction 47
Genetic Alterations in Clear Cell Ovarian Cancer 48
Clear Cell Ovarian Cancer Has Distinct Transcription Profiles 50
Differential Gene Expression in Clear Cell Adenocarcinoma of Different Organs 51
References 52
Ovarian Carcinoma: Diagnostic Immunohistochemistry of MUCIN4 (MUC4) 55
Introduction 55
Histopathology of Ovarian Cancer 56
Stages and Prognosis of Ovarian Cancer 56
Biomarkers and Screening of Ovarian Cancer 56
Aberrant Mucin Expression in Ovarian Cancer: A Novel Class of Biomarkers 57
MUCIN4: Structure and Biology 58
MUCIN4 in Ovarian Cancer 58
Methodology for MUCIN4 Immunohistochemistry 60
Tissue Sectioning 60
Immunolabeling 60
Assessment of MUCIN4 Staining 61
References 61
Distinguishing Benign from Malignant Complex Adnexal Masses in Ovarian Cancer: Two-Dimensional Power-Doppler Imaging 64
Introduction 64
Patients and Methods 65
Results 68
Discussion 69
References 72
Sertoliform Endometrioid Carcinoma of the Ovary: Diagnosis and Prognosis 99
Introduction 99
Diagnosis 99
Clinical Features 99
Gross Findings 100
Microscopic Findings 100
Differential Diagnosis 101
Immunohistochemistry 102
Cytokeratins 102
Epithelial Membrane Antigen 103
Inhibin 103
Calretinin 103
Neural Cell Adhesion Molecule (N-CAM/CD56) 104
Estrogen and Progesterone Receptors 104
Other Makers 104
Prognosis 106
References 106
Role of MUC16 (CA125) in the Pathogenesis of Epithelial Ovarian Cancer 110
Introduction 110
CA125 and MUC16 110
MUC16 in Epithelial Ovarian Cancer 112
Mesothelin and MUC16 Binding: A Model for Metastasis 112
Mesothelin 112
Mesothelin and MUC16 Binding 113
Kinetics of Mesothelin–MUC16 Binding 114
Mesothelin Binds to N-Linked Oligosaccharides Present on MUC16 115
MUC16 Binding to Natural Killer Cells: Immunosuppressive Effects 118
A Phenotypic Shift 118
NK Cell Differentiation 120
Tumor Cell Layers of Protection 121
Clear Cell Carcinoma of the Ovary: Prognosis Using Cytoreductive Surgery 124
Introduction 124
Clinical Characteristics 124
Presentation at Early Stages and Association with Endometriosis 124
Molecular Characteristics 125
Clinical Outcome 126
Resistance to Platinum-Based Chemotherapy 126
Retroperitoneal Involvement 126
Prognosis After Cytoreductive Surgery 126
Advanced Ovarian Cancer: Prediction of Surgical Outcomes Using Computed Tomography 131
Introduction 131
Value of Cytoreduction 131
Ability of Computed Tomography to Predict Optimal Cytoreduction 134
Other Techniques for Predicting Surgical Outcomes 137
Conclusion 139
References 140
Subgroups of Ovarian Carinoma: Identification Using Differential Gene Expression 75
Introduction 75
Ovarian Cancer Heterogeneity 75
Selection of Samples for Gene Microarray Analysis 76
Contamination of Gene Expression Profiles by Other Cells in Tissues 77
Number of Samples to Analyze for Gene Profiling 78
Tissue Processing Protocols 78
Importance of Pathological Quality Control 78
Clinical Correlations 79
Gene Microarray Platforms 79
RNA Isolation for Generating Gene Expression Data 79
Analysis of Gene Microarray Data 80
Need for Secondary Validation of Data 80
Goals for Gene Microarray Analysis 81
Gene Expression Analysis Used to Determine Ovarian Cancer Subgroups 81
Gene Expression Analysis Used to Compare Different Stages or Grades of Ovarian Cancer 83
Gene Expression Profiles Based on Metastasis 86
Correlation of Gene Expression Profiles to Chemotherapeutic Response 88
Correlation of Gene Expression Profiles to Surgical Debulking 91
Correlation of Gene Expression Profiles to Patients’ Survival 92
Summary 94
References 95
Renal Cell Carcinoma: Follow-Up with Magnetic Resonance Imaging After Percutaneous Radiofrequency Ablation 144
Introduction 144
Involution of the Radiofrequency Induced Thermal Ablation Zone 145
Magnetic Resonance Signal Characteristics of Radiofrequency Induced Thermal Ablation Zones 145
Residual or Recurrent Tumor 147
Metastatic Kidney Cancer: Treatment with Infusional Interleukin-2 Plus Famotidine 149
Introduction 149
Patients and Methods 149
Results 151
Discussion 151
Renal Cell Carcinoma: Preoperative Treatment with Cytokines Followed by Surgery 155
Introduction 155
Cytokines for Immunomodulation 156
Interleukin-2 (IL-2) 156
Interferon-a (IFN-a) 156
Methodological Aspects of Perioperative Immunomonitoring 157
Flow Cytometry 158
Materials 159
Methods 160
Enzyme-Linked Immunosorbent Assay 160
Materials and Methods 160
Perioperative Immunomodulation with Interleukin-2 161
Perioperative Immunomodulation with Interferon-Alpha 163
Other Agents 165
Conclusions and Future Directions 166
Metastatic Renal Cell Carcinoma: Use of Bcl-2 and Fas to Predict Responses to Immunotherapy 170
Introduction 170
Apoptotic Machinery and Tumor Cells 171
Fas-Driven Apoptosis and Bcl-2 in Renal Cell Cancer Cells 171
Bcl-2 or Fas and Prognosis of Renal Cell Cancer Patients 172
Absence of Bcl-2 and Fas/CD95/Apo-1 Predicts the Response to Immunotherapy in Metastatic Renal Cell Carcinoma 173
Clinical Course of the Patients 174
Expression of Bcl-2 174
Expression of Fas 175
Detection of Cell Proliferation and Apoptosis 175
Conclusion 176
Adenomatoid Tumor of the Adrenal Gland: Differential Diagnosis Using Immunohistochemistry 190
Introduction 190
General Features 190
Histology and Differential Diagnosis 191
Immunophenotype 192
References 194
Testicular Cancer: Post-Chemotherapy Retroperitoneal Lymph Node Dissection 195
Introduction 195
Indications for Pc-Rplnd 195
Preoperative Considerations 197
Technical Considerations 198
Treatment-Related Outcomes 201
Potential Complications 204
Postoperative Follow-Up 204
Conclusions 205
References 206
Survivors of Germ-Cell Testicular Cancer: Increased Risk of Second Primary Tumors 208
Introduction 208
Methods to Investigate Second Primary Cancers 208
Cohort Studies 208
Nested Case-Control Studies 210
Methodological Limitations 211
Second Primary Cancers Among Survivors of Testicular Cancer 212
All Testicular Cancers 212
Seminomas and Nonseminomas 213
Chemotherapy and Radiotherapy 213
References 216
Urothelial Bladder Cancer: Screening with Urine-Based Tumor Markers 221
Rationale 221
Previous Screening Programs 222
Screening in People with Occupational Exposure 222
Hematuria Screening 223
Urine-Based Tumor Markers 224
Methodological Aspects of Marker Evaluation 225
Specific Urine-Based Tumor Markers 227
Bladder Tumor Associated Antigen Test 227
Nuclear Matrix Protein-22 227
Urovysion 228
ImmunoCyt/uCyt 228
Cost-Effectiveness 229
Biases and Pitfalls in Bladder Cancer Screening 230
Future Considerations 231
Conclusions 231
Detection of OCT-4 in Bladder Cancer: Role of Cancer Stem Cell 234
Introduction 234
Materials 235
Methods 238
Human Clinical Samples 238
Total RNA Extraction 238
Analyzing the Quality of Extracted Total RNA 239
Determining the Concentration of Extracted RNA 239
Semi-Quantitative Reverse Transcription-Polymerase Chain Reaction (RT-PCR) 239
Reverse Transcription 239
PCR 239
Agarose Gel Electrophoresis 240
Western Blotting 240
Total Protein Extraction 240
Quantification of the Concentration of Extracted Protein 240
SDS-PAGE 240
Transfer 240
Blotting 241
Stripping and Reprobing the Membrane 241
Immunohistochemistry 242
Statistical Analyses 242
Results 243
Expression of OCT-4 in Tumor and Non-Tumor Tissues of Human Bladder 243
Tissue Distribution and Intracellular Localization of OCT-4 Protein in Bladder Tumors 244
Discussion 246
References 248
Uterine Cervical Glandular Lesions: Differentiation Using Immunohistochemistry of Mucins 252
Introduction 252
Materials 253
Solvents, Media, and Solutions 253
Other Materials and Equipment 254
Methods 254
Sectioning of Tissues and Slide Preparation 255
Antigen Retrieval 255
Delineating Tissue Sections 255
Inactivation of Endogenous Peroxidase 255
Blocking Non-specific Binding of Proteins 256
Primary Antibody Step 256
Amplification of Primary Antibody 256
Develop Color with Peroxidase Substrate 256
Counterstaining 256
Mounting the Tissue Specimens 257
Results 257
Discussion 259
Uterine Cervical Carcinoma: Preoperative Magnetic Resonance Imaging Staging 264
Introduction 264
Normal Anatomy of Uterine Cervix 264
General Consideration of Uterine Cervical Cancer 265
Magnetic Resonance Imaging Technique for Uterine Cervical Cancer 266
Magnetic Resonance Findings of Uterine Cervical Cancer 267
Magnetic Resonance Staging of Uterine Cervical Cancer 268
Pelvic Computed Tomography Versus Magnetic Resonance 271
Evaluation of Pelvic Lymph Nodes 272
References 273
Cancer Imaging and Intracavitary Brachytherapy for Cervical Cancer 276
Introduction 276
Intracavitary Brachytherapy for Cervical Cancer 277
Applicator Insertion 277
Dose Specification 277
Magnetic Resonance Imaging for Cervical Cancer Brachytherapy 278
Image-Based Brachytherapy 279
References 280
Cervical Cancer: Methods for Assessing the Quality of Life 282
Concept of Quality of Life 282
Selecting Appropriate Quality of Life Measurements 283
First Step: Questions to Be Asked When Selecting a Quality of Life Instrument 283
Second Step: Introducing a Quality of Life Instrument in Clinical Practice 284
Psychometric Properties of a Quality of Life Instrument 284
Reliability 284
Validity 284
Responsiveness to Change 285
Types of Qualty of Life Measurments 285
Development and Cross-Cultural Validation of Quality of Life Instruments 287
EORTC Modular Approach to Quality of Life Assessment 287
Development of the Cervical Cancer Module (EORTC QLQ-CX24) 288
Phase I: Generation of QoL Issues 288
Phase II: Construction of Items and Translation 288
Phase III: Pretesting 288
Phase IV: Testing the Psychometric Properties 289
References 290
Cervical Cancer: Positron Emission Tomography and Positron Emission Tomography/Computed Tomography 293
Introduction 293
Background and Staging 293
Directing Therapy 297
Prognosis 298
Posttherapy Monitoring 299
References 300
Endometrial Cancer: Indoleamine 2,3-Dioxygenase as a Prognostic Indicator 303
Introduction 303
Materials and Methods 305
Antibodies 305
Patients 305
Immunohistochemical Staining 306
Evaluation of Indoleamine 2,3-Dioxygenase Expression 306
Statistical Analysis 306
Results 307
Immunohistochemical Expression of IDO in Endometrial Cancer Tissues 307
Association of IDO Expression with the Patient Survival 308
Multivariate Analysis of Prognostic Variables in Endometrial Cancer Patients 308
Discussion 309
References 311
Neurofibromatosis Type 1-Associated Malignant Melanoma: Molecular Evidence of Inactivation of the NF1 Gene 316
Introduction 316
Methodology 317
Definition of Cancer Genes 317
Identification of Genes Implicated in Oncogenesis 317
Role of NF1 Gene Mutations in NF1-Associated Melanoma 319
Melanoma Incidence in NF1 319
Biologic Role of Neurofibromin in Melanocytes 319
Mutations of the NF1 Gene in NF1-Associated Malignant Melanoma 320
Inactivation of the NF1 Gene in NF1-Associated Malignant Melanoma 321
Conclusion 322
Malignant Melanoma: Localisation and Characterization Using Fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography 325
Introduction and Clinical Background 325
Potential Indications of Fluorodeoxyglucose Positron Emission Tomography Imaging in the Management of Malignant Melanoma 326
Detection of Locoregional Lymph Node Invasion 327
Detection of Distant Metastases 328
Pitfalls and Additional Value of Integrated PET/CT Imaging 328
Role of FDG-PET in Monitoring Response to Therapy 331
Role of FDG-PET in Patient Management 332
Alternative Tracers for Diagnosing MM and Monitoring Therapy Response 332
References 335
Malignant Melanoma Versus Deep Penetrating Nevus: Diagnostic and Prognostic Immunohistochemistry of Dipeptidyl Peptidase IV ( 337
Introduction 337
The Deep Penetrating Nevus as a Model of Paradoxical Melanocytic Invasion 337
Common Melanoma Markers Fail to Separate Between Melanocytic Invasion and True Melanocytic Malignancy 338
Immunostaining of Dipeptidyl Peptidase IV Discriminates Metastatic Malignant Melanoma from Deep Penetrating Nevus – Applicatio 338
Tissue Sample Collection and Immunohistochemistry 339
Immunohistochemical Evaluation 339
Discussion and Biologic Background 341
References 344
Nonmelanoma Skin Cancer: Use of Epha1 Receptor as a Prognostic Marker 346
The Eph/Ephrin Family 346
Eph/Ephrin Expression in Adult Human Tissues 347
Eph/Ephrin Expression in Human Skin 347
Epha1 and Nonmelanoma Skin Cancer 349
References 351
Pretreated Chronic Lymphocytic Leukemia: Use of Alemtuzumab 355
Introduction 355
Evolution of Treatments for Chronic Lypmpho­cytic Leukemia 356
Alemtuzumab as Monotherapy in Pretreated Chronic Lymphocytic Leukemia 356
Combination Therapy 362
Consolidation Therapy with Alemtuzumab 364
References 366
Immunotherapeutic Strategies, Radiotherapy, and Targeted Radionuclide Therapy Approaches for the Treatment of Multiple Myeloma 372
Introduction 372
Therapeutic Strategies in Multiple Myeloma 373
Immunotherapy 373
Monoclonal Antibodies 373
Anti-IL-6 Therapy 374
Strategies for Targeting IGF-1 376
Immunotoxins and Immunoconjugates 377
Radioimmunoconjugates 378
Myeloma Vaccines 379
Growth Factors 380
Manipulation of Immune Cells (Cell Therapy) 381
Thalidomide and Immunomodulatory Drugs 381
Radiotherapy 382
Targeted Radiotherapy 384
Bone Seeking Radiopharmaceuticals 384
Skeletal Targeted Radiotherapy 385
Mechanism of Action of STR 385
Clinical Trials of 166Ho-DOTMP 386
Phase I/II Dosimetry Study 386
Phase III Pivotal Trial 388
Ongoing Phase III Trials 388
Conclusion and Perspectives 389
References 390
Low Grade Fibromyxoid Sarcoma: Diagnosis by Detecting FUS-CREB3L2 Fusion Gene Using Reverse Transcription–Polymerase Chain Reac 396
Introduction 396
Detection of the FUS-CREB3l2 Fusion Transcripts Using Formalin-Fixed, Paraffin-Embedded Tumor Tissue 397
Primers 397
RNA Extraction 398
RT-PCR 398
Sequence Analysis 399
Results 399
Evaluation of the RT-PCR Results 400
References 401
Synovial Sarcoma: Role of TLE1 as a Diagnostic Immunohistochemical Marker 402
Introduction 402
Materials 404
Methods 405
Manual Immunostaining 405
Automated Immunostaining 406
Interpretation of TLE Staining 407
Results and Discussion 407
References 410
The Immunohistochemistry of Kaposi’s Sarcoma 413
Introduction 413
Materials 415
Methods 416
Interpretation 425
Histogenesis 426
Pathogenesis 429
HHV8 Infection 429
Angiogenesis 430
Chemokines 431
Apoptosis 431
Diagnosis 432
Therapy 432
Conclusion 433
Synovial Sarcoma: Role of Immunohistochemistry and Molecular Genetics in Diagnosis and Prognosis 440
Introduction 440
Diagnosis 441
Histology 441
Ultrastructure 443
Immunohistochemistry 443
Cytogenetics and Molecular Genetics 445
Cytogenetics 446
In Situ hybridization 446
Polymerase Chain Reaction (PCR) 448
Prognostic Markers for Synovial Sarcoma 449
Sarcoma: Treatment with Ecteinascidin-743 456
Introduction 456
Mechanisms of Action and Resistance 457
Binding to DNA 457
Inhibition of Transcription Factors 457
Inhibition of DNA Repair Machinery 458
Other Effects 459
Metabolism and Toxicity of ET-743 459
Clinical Activity of ET-743 in Patients with Sarcoma 461
ET-743 in Combination with Other Drugs 463
References 463
Wilms Tumor: Prognosis Using Microvessel Density 179
Introduction 179
Prognostic Factors in Wilms Tumor 179
Angiogenesis 180
Quantification Methods 180
Angiogenesis and Wilms Tumor 182
References 185