Methods of Cancer Diagnosis, Therapy, and Prognosis - Ovarian Cancer, Renal Cancer, Urogenitary tract Cancer, Urinary Bladder Cancer, Cervical Uterine Cancer, Skin Cancer, Leukemia, Multiple Myeloma and Sarcoma

Contributors

Preface

Introduction

Identification of Biomarkers for Clear Cell Ovarian Adenocarcinoma

Introduction

Genetic Alterations in Clear Cell Ovarian Cancer

Clear Cell Ovarian Cancer Has Distinct Transcription Profiles

Differential Gene Expression in Clear Cell Adenocarcinoma of Different Organs

References

Ovarian Carcinoma: Diagnostic Immunohistochemistry of MUCIN4 (MUC4)

Introduction

Histopathology of Ovarian Cancer

Stages and Prognosis of Ovarian Cancer

Biomarkers and Screening of Ovarian Cancer

Aberrant Mucin Expression in Ovarian Cancer: A Novel Class of Biomarkers

MUCIN4: Structure and Biology

MUCIN4 in Ovarian Cancer

Methodology for MUCIN4 Immunohistochemistry

Tissue Sectioning

Immunolabeling

Assessment of MUCIN4 Staining

References

Distinguishing Benign from Malignant Complex Adnexal Masses in Ovarian Cancer: Two-Dimensional Power-Doppler Imaging

Introduction

Patients and Methods

Results

Discussion

References

Sertoliform Endometrioid Carcinoma of the Ovary: Diagnosis and Prognosis

Introduction

Diagnosis

Clinical Features

Gross Findings

Microscopic Findings

Differential Diagnosis

Immunohistochemistry

Cytokeratins

Epithelial Membrane Antigen

Inhibin

Calretinin

Neural Cell Adhesion Molecule (N-CAM/CD56)

Estrogen and Progesterone Receptors

Other Makers

Prognosis

References

Role of MUC16 (CA125) in the Pathogenesis of Epithelial Ovarian Cancer

Introduction

CA125 and MUC16

MUC16 in Epithelial Ovarian Cancer

Mesothelin and MUC16 Binding: A Model for Metastasis

Mesothelin

Mesothelin and MUC16 Binding

Kinetics of Mesothelin–MUC16 Binding

Mesothelin Binds to N-Linked Oligosaccharides Present on MUC16

MUC16 Binding to Natural Killer Cells: Immunosuppressive Effects

A Phenotypic Shift

NK Cell Differentiation

Tumor Cell Layers of Protection

Clear Cell Carcinoma of the Ovary: Prognosis Using Cytoreductive Surgery

Introduction

Clinical Characteristics

Presentation at Early Stages and Association with Endometriosis

Molecular Characteristics

Clinical Outcome

Resistance to Platinum-Based Chemotherapy

Retroperitoneal Involvement

Prognosis After Cytoreductive Surgery

Advanced Ovarian Cancer: Prediction of Surgical Outcomes Using Computed Tomography

Introduction

Value of Cytoreduction

Ability of Computed Tomography to Predict Optimal Cytoreduction

Other Techniques for Predicting Surgical Outcomes

Conclusion

References

Subgroups of Ovarian Carinoma: Identification Using Differential Gene Expression

Introduction

Ovarian Cancer Heterogeneity

Selection of Samples for Gene Microarray Analysis

Contamination of Gene Expression Profiles by Other Cells in Tissues

Number of Samples to Analyze for Gene Profiling

Tissue Processing Protocols

Importance of Pathological Quality Control

Clinical Correlations

Gene Microarray Platforms

RNA Isolation for Generating Gene Expression Data

Analysis of Gene Microarray Data

Need for Secondary Validation of Data

Goals for Gene Microarray Analysis

Gene Expression Analysis Used to Determine Ovarian Cancer Subgroups

Gene Expression Analysis Used to Compare Different Stages or Grades of Ovarian Cancer

Gene Expression Profiles Based on Metastasis

Correlation of Gene Expression Profiles to Chemotherapeutic Response

Correlation of Gene Expression Profiles to Surgical Debulking

Correlation of Gene Expression Profiles to Patients’ Survival

Summary

References

Renal Cell Carcinoma: Follow-Up with Magnetic Resonance Imaging After Percutaneous Radiofrequency Ablation

Introduction

Involution of the Radiofrequency Induced Thermal Ablation Zone

Magnetic Resonance Signal Characteristics of Radiofrequency Induced Thermal Ablation Zones

Residual or Recurrent Tumor

Metastatic Kidney Cancer: Treatment with Infusional Interleukin-2 Plus Famotidine

Introduction

Patients and Methods

Results

Discussion

Renal Cell Carcinoma: Preoperative Treatment with Cytokines Followed by Surgery

Introduction

Cytokines for Immunomodulation

Interleukin-2 (IL-2)

Interferon-a (IFN-a)

Methodological Aspects of Perioperative Immunomonitoring

Flow Cytometry

Materials

Methods

Enzyme-Linked Immunosorbent Assay

Materials and Methods

Perioperative Immunomodulation with Interleukin-2

Perioperative Immunomodulation with Interferon-Alpha

Other Agents

Conclusions and Future Directions

Metastatic Renal Cell Carcinoma: Use of Bcl-2 and Fas to Predict Responses to Immunotherapy

Introduction

Apoptotic Machinery and Tumor Cells

Fas-Driven Apoptosis and Bcl-2 in Renal Cell Cancer Cells

Bcl-2 or Fas and Prognosis of Renal Cell Cancer Patients

Absence of Bcl-2 and Fas/CD95/Apo-1 Predicts the Response to Immunotherapy in Metastatic Renal Cell Carcinoma

Clinical Course of the Patients

Expression of Bcl-2

Expression of Fas

Detection of Cell Proliferation and Apoptosis

Conclusion

Adenomatoid Tumor of the Adrenal Gland: Differential Diagnosis Using Immunohistochemistry

Introduction

General Features

Histology and Differential Diagnosis

Immunophenotype

References

Testicular Cancer: Post-Chemotherapy Retroperitoneal Lymph Node Dissection

Introduction

Indications for Pc-Rplnd

Preoperative Considerations

Technical Considerations

Treatment-Related Outcomes

Potential Complications

Postoperative Follow-Up

Conclusions

References

Survivors of Germ-Cell Testicular Cancer: Increased Risk of Second Primary Tumors

Introduction

Methods to Investigate Second Primary Cancers

Cohort Studies

Nested Case-Control Studies

Methodological Limitations

Second Primary Cancers Among Survivors of Testicular Cancer

All Testicular Cancers

Seminomas and Nonseminomas

Chemotherapy and Radiotherapy

References

Urothelial Bladder Cancer: Screening with Urine-Based Tumor Markers

Rationale

Previous Screening Programs

Screening in People with Occupational Exposure

Hematuria Screening

Urine-Based Tumor Markers

Methodological Aspects of Marker Evaluation

Specific Urine-Based Tumor Markers

Bladder Tumor Associated Antigen Test

Nuclear Matrix Protein-22

Urovysion

ImmunoCyt/uCyt

Cost-Effectiveness

Biases and Pitfalls in Bladder Cancer Screening

Future Considerations

Conclusions

Detection of OCT-4 in Bladder Cancer: Role of Cancer Stem Cell

Introduction

Materials

Methods

Human Clinical Samples

Total RNA Extraction

Analyzing the Quality of Extracted Total RNA

Determining the Concentration of Extracted RNA

Semi-Quantitative Reverse Transcription-Polymerase Chain Reaction (RT-PCR)

Reverse Transcription

PCR

Agarose Gel Electrophoresis

Western Blotting

Total Protein Extraction

Quantification of the Concentration of Extracted Protein

SDS-PAGE

Transfer

Blotting

Stripping and Reprobing the Membrane

Immunohistochemistry

Statistical Analyses

Results

Expression of OCT-4 in Tumor and Non-Tumor Tissues of Human Bladder

Tissue Distribution and Intracellular Localization of OCT-4 Protein in Bladder Tumors

Discussion

References

Uterine Cervical Glandular Lesions: Differentiation Using Immunohistochemistry of Mucins

Introduction

Materials

Solvents, Media, and Solutions

Other Materials and Equipment

Methods

Sectioning of Tissues and Slide Preparation

Antigen Retrieval

Delineating Tissue Sections

Inactivation of Endogenous Peroxidase

Blocking Non-specific Binding of Proteins

Primary Antibody Step

Amplification of Primary Antibody

Develop Color with Peroxidase Substrate

Counterstaining

Mounting the Tissue Specimens

Results

Discussion

Uterine Cervical Carcinoma: Preoperative Magnetic Resonance Imaging Staging

Introduction

Normal Anatomy of Uterine Cervix

General Consideration of Uterine Cervical Cancer

Magnetic Resonance Imaging Technique for Uterine Cervical Cancer

Magnetic Resonance Findings of Uterine Cervical Cancer

Magnetic Resonance Staging of Uterine Cervical Cancer

Pelvic Computed Tomography Versus Magnetic Resonance

Evaluation of Pelvic Lymph Nodes

References

Cancer Imaging and Intracavitary Brachytherapy for Cervical Cancer

Introduction

Intracavitary Brachytherapy for Cervical Cancer

Applicator Insertion

Dose Specification

Magnetic Resonance Imaging for Cervical Cancer Brachytherapy

Image-Based Brachytherapy

References

Cervical Cancer: Methods for Assessing the Quality of Life

Concept of Quality of Life

Selecting Appropriate Quality of Life Measurements

First Step: Questions to Be Asked When Selecting a Quality of Life Instrument

Second Step: Introducing a Quality of Life Instrument in Clinical Practice

Psychometric Properties of a Quality of Life Instrument

Reliability

Validity

Responsiveness to Change

Types of Qualty of Life Measurments

Development and Cross-Cultural Validation of Quality of Life Instruments

EORTC Modular Approach to Quality of Life Assessment

Development of the Cervical Cancer Module (EORTC QLQ-CX24)

Phase I: Generation of QoL Issues

Phase II: Construction of Items and Translation

Phase III: Pretesting

Phase IV: Testing the Psychometric Properties

References

Cervical Cancer: Positron Emission Tomography and Positron Emission Tomography/Computed Tomography

Introduction

Background and Staging

Directing Therapy

Prognosis

Posttherapy Monitoring

References

Endometrial Cancer: Indoleamine 2,3-Dioxygenase as a Prognostic Indicator

Introduction

Materials and Methods

Antibodies

Patients

Immunohistochemical Staining

Evaluation of Indoleamine 2,3-Dioxygenase Expression

Statistical Analysis

Results

Immunohistochemical Expression of IDO in Endometrial Cancer Tissues

Association of IDO Expression with the Patient Survival

Multivariate Analysis of Prognostic Variables in Endometrial Cancer Patients

Discussion

References

Neurofibromatosis Type 1-Associated Malignant Melanoma: Molecular Evidence of Inactivation of the NF1 Gene

Introduction

Methodology

Definition of Cancer Genes

Identification of Genes Implicated in Oncogenesis

Role of NF1 Gene Mutations in NF1-Associated Melanoma

Melanoma Incidence in NF1

Biologic Role of Neurofibromin in Melanocytes

Mutations of the NF1 Gene in NF1-Associated Malignant Melanoma

Inactivation of the NF1 Gene in NF1-Associated Malignant Melanoma

Conclusion

Malignant Melanoma: Localisation and Characterization Using Fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography

Introduction and Clinical Background

Potential Indications of Fluorodeoxyglucose Positron Emission Tomography Imaging in the Management of Malignant Melanoma

Detection of Locoregional Lymph Node Invasion

Detection of Distant Metastases

Pitfalls and Additional Value of Integrated PET/CT Imaging

Role of FDG-PET in Monitoring Response to Therapy

Role of FDG-PET in Patient Management

Alternative Tracers for Diagnosing MM and Monitoring Therapy Response

References

Malignant Melanoma Versus Deep Penetrating Nevus: Diagnostic and Prognostic Immunohistochemistry of Dipeptidyl Peptidase IV (

Introduction

The Deep Penetrating Nevus as a Model of Paradoxical Melanocytic Invasion

Common Melanoma Markers Fail to Separate Between Melanocytic Invasion and True Melanocytic Malignancy

Immunostaining of Dipeptidyl Peptidase IV Discriminates Metastatic Malignant Melanoma from Deep Penetrating Nevus – Applicatio

Tissue Sample Collection and Immunohistochemistry

Immunohistochemical Evaluation

Discussion and Biologic Background

References

Nonmelanoma Skin Cancer: Use of Epha1 Receptor as a Prognostic Marker

The Eph/Ephrin Family

Eph/Ephrin Expression in Adult Human Tissues

Eph/Ephrin Expression in Human Skin

Epha1 and Nonmelanoma Skin Cancer

References

Pretreated Chronic Lymphocytic Leukemia: Use of Alemtuzumab

Introduction

Evolution of Treatments for Chronic Lypmpho­cytic Leukemia

Alemtuzumab as Monotherapy in Pretreated Chronic Lymphocytic Leukemia

Combination Therapy

Consolidation Therapy with Alemtuzumab

References

Immunotherapeutic Strategies, Radiotherapy, and Targeted Radionuclide Therapy Approaches for the Treatment of Multiple Myeloma

Introduction

Therapeutic Strategies in Multiple Myeloma

Immunotherapy

Monoclonal Antibodies

Anti-IL-6 Therapy

Strategies for Targeting IGF-1

Immunotoxins and Immunoconjugates

Radioimmunoconjugates

Myeloma Vaccines

Growth Factors

Manipulation of Immune Cells (Cell Therapy)

Thalidomide and Immunomodulatory Drugs

Radiotherapy

Targeted Radiotherapy

Bone Seeking Radiopharmaceuticals

Skeletal Targeted Radiotherapy

Mechanism of Action of STR

Clinical Trials of 166Ho-DOTMP

Phase I/II Dosimetry Study

Phase III Pivotal Trial

Ongoing Phase III Trials

Conclusion and Perspectives

References

Low Grade Fibromyxoid Sarcoma: Diagnosis by Detecting FUS-CREB3L2 Fusion Gene Using Reverse Transcription–Polymerase Chain Reac

Introduction

Detection of the FUS-CREB3l2 Fusion Transcripts Using Formalin-Fixed, Paraffin-Embedded Tumor Tissue

Primers

RNA Extraction

RT-PCR

Sequence Analysis

Results

Evaluation of the RT-PCR Results

References

Synovial Sarcoma: Role of TLE1 as a Diagnostic Immunohistochemical Marker

Introduction

Materials

Methods

Manual Immunostaining

Automated Immunostaining

Interpretation of TLE Staining

Results and Discussion

References

The Immunohistochemistry of Kaposi’s Sarcoma

Introduction

Materials

Methods

Interpretation

Histogenesis

Pathogenesis

HHV8 Infection

Angiogenesis

Chemokines

Apoptosis

Diagnosis

Therapy

Conclusion

Synovial Sarcoma: Role of Immunohistochemistry and Molecular Genetics in Diagnosis and Prognosis

Introduction

Diagnosis

Histology

Ultrastructure

Immunohistochemistry

Cytogenetics and Molecular Genetics

Cytogenetics

In Situ hybridization

Polymerase Chain Reaction (PCR)

Prognostic Markers for Synovial Sarcoma

Sarcoma: Treatment with Ecteinascidin-743

Introduction

Mechanisms of Action and Resistance

Binding to DNA

Inhibition of Transcription Factors

Inhibition of DNA Repair Machinery

Other Effects

Metabolism and Toxicity of ET-743

Clinical Activity of ET-743 in Patients with Sarcoma

ET-743 in Combination with Other Drugs

References

Wilms Tumor: Prognosis Using Microvessel Density

Introduction

Prognostic Factors in Wilms Tumor

Angiogenesis

Quantification Methods

Angiogenesis and Wilms Tumor

References