Methods of Cancer Diagnosis, Therapy, and Prognosis

Methods of Cancer Diagnosis, Therapy, and Prognosis

Volume 7

For other titles published in this series, go towww.springer.com/series/8172

Methods of Cancer Diagnosis, Therapy, and Prognosis

Volume 7

Methods of Cancer Diagnosis, Therapy, and PrognosisGeneral Overviews, Head and Neck Cancer and Thyroid Cancer

Edited by

M.A. HayatDepartment of Biological Sciences,Kean University, Union, NJ, USA

ISBN 978-90-481-3185-3 e-ISBN 978-90-481-3186-0

Library of Congress Control Number: 2009941464

© 2010 Springer Science + Business Media B.V.No part of this work may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, microfi lming, recording or otherwise, without written permission from the Publisher, with the exception of any material supplied specifi cally for the purpose of being entered and executed on a computer system, for exclusive use by the purchaser of the work.

Printed on acid-free paper

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EditorM.A. HayatDepartment of Biological SciencesKean UniversityUnion, NJ, USA

New technology, for better or for worse, will be used, as that is our nature.

Lewis Thomas

You have been given the key that opens the gates of heaven; the same key opens the gates of hell.

Writing at the entrance to a Buddhist temple

vii

Contributors

Domenico Adorno Instituto CNR per I Trapianti d’Organo e l’Immunocitologia (ITOI)-P.le Collemaggio-67100 L’Aquila, Italy

Huguette Albrecht School of Medicine, Division of Hematology and Oncology, UCDMC Cancer Center, 2800 Bidwell St #3, Davis, CA 95618, USA

Katsuyuki Aozasa Department of Pathology, Osaka University School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan

Enke Baldini Department of Experimental Medicine, Section of Endocrinology, “Sapienza” University of Rome, Viale del Policlinico, 155, 00161 Rome, Italy

Aubin Balmer Hopital Ophtalmique Jules Gonin, Avenue de France 15, 1004 Lausanne, Switzerland

Niall Barron National Institute for Cellular Biotechnology, Dublin City University, Glasnevin, Dublin 9, Ireland

Mirco Bartolomei Division of Nuclear Medicine, European Institute of Oncology, via Ripamonti 435, 20141, Milan, Italy

Martin Béhé Department of Nuclear Medicine, University Hospital Giessen and Marburg, Campus Marburg, Baldingerstasse, 35042 Marburg, Germany

Thomas M. Behr Department of Nuclear Medicine, University Hospital Giessen and Marburg, Campus Marburg, Baldingerstasse, 35042 Marburg, Germany

Anna Maria Berghella Instituto CNR per I Trapianti d’Organo e l’Immunocitologia (ITOI)-P.le Collemaggio-67100 L’Aquila, Italy

Donald Bodenner Division of Geriatric Endocrinology, Department of Geriatrics, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA

A.H. Brouwers Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, Groningen, P.O. Box 20.001 9700 RB Groningen, the Netherlands

viivii

viii Contributors

Marco Chinol Division of Nuclear Medicine, European Institute of Oncology, via Ripamonti 435, 20141, Milan, Italy

William C.S. Cho Department of Clinical Oncology, Queen Elizabeth Hospital, Room 1305, 13/F, Block R, 30 Gascoigne Road, Kowloon, Hong Kong, SAR

Brett Clarke Department of Otolaryngology-Head and Neck Surgery, University of Arkansas for Medical Sciences, 4301 W. Markham Street, Suite 543, Little Rock, AR 77205-7199, USA

Martin Clynes National Institute for Cellular Biotechnology, Dublin City University, Glasnevin, Dublin 9, Ireland

Ida Contasta Instituto CNR per I Trapianti d’Organo e l’Immunocitologia (ITOI)-P.le Collemaggio-67100 L’Aquila, Italy

Marta Cremonesi Division of Health Physics, European Institute of Oncology, via Ripamonti 435, 20141, Milan, Italy

Massimino D’Armiento Department of Experimental Medicine, Section of Endocrinology, “Sapienza” University of Rome, Viale del Policlinico, 155, 00161 Rome, Italy

Hanna Dahlstrand Department of Otorhinolaryngology Head and Neck Surgery, Karolinska University Hospital, 171 76 Stockholm, Sweden

Yeumeng Dai Department of Otolaryngology-Head and Neck Surgery, University of Arkansas for Medical Sciences, 4301 W. Markham Street, Suite 543, Little Rock, AR 77205-7199, USA

Lioe-Fee de Geus-Oei Department of Nuclear Medicine, Radboud University Nijmegen Medical Center, Postbus 9101, 6500 HB Nijmegen, the Netherlands

Tiziana Del Beato Instituto CNR per I Trapianti d’Organo e l’Immunocitologia (ITOI)-P.le Collemaggio-67100 L’Aquila, Italy

Padraig Doolan National Institute for Cellular Biotechnology, Dublin City University, Glasnevin, Dublin 9, Ireland

Mahila Ferrari Division of Health Physics, European Institute of Oncology, via Ripamonti 435, 20141, Milan, Italy

Stephen P. Finn Center for Molecular Oncologic Pathology and Loda Lab, Room JF215H, Jimmy Fund Building, Dana Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA

Sophie D. Fosså Department of Clinical Cancer Research, Rikshospitalet-Radiumhospitalet Medical Center, Oslo, Norway

Contributors ix

Alex Gaither Developmental and Molecular Research, Novartis Institutes for Biomedical Research, 500 Technology Square, Cambridge, MA 02139, USA

Lucia Garaboldi Division of Nuclear Medicine, European Institute of Oncology, via Ripamonti 435, 20141, Milan, Italy

Martin Gotthardt Department of Nuclear Medicine, Radboud University Nijmegen Medical Center, Postbus 9101, 6500 HB Nijmegen, the Netherlands

Chiara Maria Grana Division of Nuclear Medicine, European Institute of Oncology, via Ripamonti 435, 20141, Milan, Italy

Obi L. Griffi th Michael Smith Genome Sciences Center, British Columbia Cancer Agency, Vancouver, V5Z 1L3, Canada

Lalle Hammarstedt Department of Otorhinolaryngology Head and Neck Surgery, Karolinska University Hospital, 171 76 Stockholm, Sweden

Steven J.M. Jones Michael Smith Genome Sciences Center, British Columbia Cancer Agency, Vancouver, V5Z 1L3, Canada

Mathew C. Kiernan Institute of Neurological Science, Princes of Wales Hospital, Prince of Wales Medical Research Institute, University of New South Wales, Randwick NSW 2031, Australia

Deanne King Department of Otolaryngology-Head and Neck Surgery, Thyroid Clinic, Arkansas Cancer Research Center, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA

K.P. Koopsmans Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, Groningen, P.O. Box 20.001 9700 RB Groningen, the Netherlands

Wooin Lee Department of Medicine, Division of Hematology and Oncology, Vanderbilt University, 777 Preston Research Building, 2220 Pierce Avenue, Nashville, TN 37232, USA

Li Li State Key Laboratory in Southern China, Imaging Diagnosis and Interventional Center, Cancer Center, Sun Yat-sen University, 651 Dongfeng Dong Road, Guangzhou 510060, Guang Dong, People’s Republic of China

T.P. Links Department of Endocrinology, University Medical Center Groningen, Groningen, P.O. Box 20.001 9700 RB Groningen, the Netherlands

Li-Zhi Liu State Key Laboratory in Southern China, Imaging Diagnosis and Interventional Center, Cancer Center, Sun Yat-sen University, 651 Dongfeng Dong Road, Guangzhou 510060, Guang Dong, People’s Republic of China

x Contributors

Craig Lockhart Division of Oncology, Washington University in St. Louis School of Medicine, Developmental Therapeutics Program, Siteman Cancer Center, 660 South Euclid Avenue, Campus Box 8007, St. Louis, MO 63110, USA

Jeffrey P. MacKeigan Laboratory of Systems Biology, Van Andel Research Institute, 333 Bostwick Ave, Grand Rapids, MI 49503, USA

John R. Mackey Department of Internal Medicine, Hotel Dieu, 1 place de l’Hôpital, 69288 Lyon Cedex 02, France

Luigi Martano Division of Nuclear Medicine, European Institute of Oncology, via Ripamonti 435, 20141, Milan, Italy

Joshua McElderry Department of Otolaryngology-Head and Neck Surgery, University of Arkansas for Medical Sciences, 4301 W. Markham Street, Suite 543, Little Rock, AR 77205-7199, USA

Jai Prakash Mehta National Institute for Cellular Biotechnology, Dublin City University, Glasnevin, Dublin 9, Ireland

Adrienne Melck Department of Surgery, University of British Columbia, 910 West 10th Avenue, Vancouver, B.C., Canada V5Z 4E3

Rahmawati Minhajat Department of Pathology and Biodefense, Faculty of Medicine, Saga University, Nabeshima 5-1-1, Saga City, Saga 849-8501 Japan

Daisuke Mori Department of Pathology and Biodefense, Faculty of Medicine, Saga University, Nabeshima 5-1-1, Saga City, Saga 849-8501 Japan

Eiichi Morii Department of Pathology, Osaka University School of Medicine, 2-2 Yamada-oka, Suita, Osaka, 565-0871 Japan

Sanjay Mukhopadhyay Department of Pathology, State University of New York Upstate Medical University, 750 E. Adams Street, Syracuse, NY 13210, USA

Eva Munck-Wikland Department of Otorhinolaryngology Head and Neck Surgery, Karolinska University Hospital, 171 76 Stockholm, Sweden

Francis Munier Hopital Ophtalmique Jules Gonin, Avenue de France 15, 1004 Lausanne, Switzerland

Takashi Nakamura Department of Radiology and Cancer Biology, Nagasaki University School of Dentistry, Sakamoto 1-7-1, Nagasaki 852-8588, Japan

Michel R. Nasr Department of Pathology, University of Iowa Hospitals and Clinics, 200 Hawkins Dr., 6227 RCO, Iowa City, IA 52242, USA

Lorraine O’Driscoll National Institute for Cellular Biotechnology, Dublin City University, Glasnevin, Dublin 9, Ireland

Contributors xi

Jan Oldenburg Department of Clinical Cancer Research, Rikshospitalet-Radiumhospitalet Medical Center, Oslo, Norway

John J. O’Leary Center for Molecular Oncologic Pathology and Loda Lab, Room JF215H, Jimmy Fund Building, Dana Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA

Giovanni Paganelli Division of Nuclear Medicine, European Institute of Oncology, via Ripamonti 435, 20141, Milan, Italy

Stefano Papi Division of Nuclear Medicine, European Institute of Oncology, via Ripamonti 435, 20141, Milan, Italy

Sussana B. Park The University of New South Wales, Institute of Neurological Sciences, The Prince of Wales Hospital, Prince of Wales Medical Research Institute, Randwick NSW 2031, Australia

Patrizia Pellegrini Instituto CNR per I Trapianti d’Organo e l’Immunocitologia (ITOI)-P.le Collemaggio-67100 L’Aquila, Italy

T.T.H. Phan Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, Groningen, P.O. Box 20.001 9700 RB Groningen, the Netherlands

Selina Raguz MRC Clinical Services Centre Imperial College Faculty of Medicine, Hammersmith Hospital, Du Cane Road, London W12 0NN, United Kingdom

Laura Ravasi Division of Nuclear Medicine, European Institute of Oncology, via Ripamonti 435, 20141, Milan, Italy

Sanziana A. Roman Yale University School of Medicine, 333 Cedar Street, P.O. Box 208062, New Haven, CT 06520-8062, USA

Rahel Sahli Department of Endocrinology and Diabetology, University Hospital Bern, Switzerland

Pascal Sève Department of Internal Medicine, Hotel Dieu, 1 place de l’Hôpital, 69288 Lyon Cedex 02, France

Neelam G. Shah The Gujarat Cancer and Research Institute, NCH Compound, Aswara, Ahmedabad 380 016, Gujarat, India

Orla M. Sheils Center for Molecular Oncologic Pathology and Loda Lab, Room JF215H, Jimmy Fund Building, Dana Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA

Julie Ann Sosa Yale University School of Medicine, 333 Cedar Street, P.O. Box 208062, New Haven, CT 06520-8062, USA

xii Contributors

Brendan C. Stack Jr., Department of Otolaryngology-Head and Neck Surgery, University of Arkansas for Medical Sciences, 4301 W. Markham Street, Suite 543, Little Rock, AR 77205-7199, USA

Misa Sumi Department of Radiology and Cancer Biology, Nagasaki University School of Dentistry, Sakamoto 1-7-1, Nagasaki 852-8588, Japan

Osamu Tokunaga Department of Pathology and Biodefense, Faculty of Medicine, Saga University, Nabeshima 5-1-1, Saga City, Saga 849-8501 Japan

T.I. Trivedi The Gujarat Cancer and Research Institute, NCH Compound, Aswara, Ahmedabad 380 016, Gujarat, India

Salvatore Ulisse Department of Experimental Medicine, Section of Endocrinology, “Sapienza” University of Rome, Viale del Policlinico, 155, 00161 Rome, Italy

Istvan Vajtai Section of Neuropathology, Institute of Pathology, University of Bern, Murtenstrasse 31, P.O. Box 62, CH-3010 Bern, Switzerland

Marc Van Cauteren Department of Radiology andCancer Biology, Nagasaki University School of Dentistry, Sakamoto 1-7-1, Nagasaki 852-8588, Japan

H.H.G. Verbeek Department of Endocrinology, University Medical Center Groningen, Groningen, P.O. Box 20.001 9700 RB Groningen, the Netherlands

Tracy S. Wang Yale University School of Medicine, 333 Cedar Street, P.O. Box 208062, New Haven, CT 06520-8062, USA

Sam M. Wiseman Saint Paul’s Hospital, Department of Surgery, Room C303, Burrard Bldg, 1081 Burrard Street, Vancouver, BC V6Z1Y6 Canada

David T. Wong UIC College of Dentistry, CMBOD (MC860), 801 S. Paulina Street, Room 530C, Chicago, IL 60612-7213, USA

Ernesto Yagüe Department of Oncology, Division of Surgery, Oncology, Reproductive Biology and Anaesthetics, Imperial College Faculty of Medicine, Hammersmith Hospital, Du Cane Road, London W12 0NN, United Kingdom

Ichiro Yasuda First Department of Internal Medicine, Gifu University Hospital, 1-1 Yanagido, Gifu 501-1194, Japan

Jian-Hui Ye Department Otolaryngology-Head and Neck Surgery, University of Arkansas for Medical Sciences, 4301 W. Markham Street, Suite 543, Little Rock, AR 77205-7199, USA

Contributors xiii

Tianwei Yu UIC College of Dentistry, CMBOD (MC860), 801 S. Paulina Street, Room 530C, Chicago, IL 60612-7213, USA

Xiaofeng Zhou UIC College of Dentistry, CMBOD (MC860), 801 S. Paulina Street, Room 530C, Chicago, IL 60612-7213, USA

Leonidas Zografos Hopital Ophtalmique Jules Gonin, Avenue de France 15, 1004 Lausanne, Switzerland

Preface

There are more than 100 types of cancers affecting all parts of the human body. More than 11 million people are diagnosed with cancer every year, and it is estimated that there will be 16 million new cases by the year 2020. In 2005, 7.6 million peo-ple died of cancer, that is, 13% of the 58 million deaths worldwide. It is estimated that 9 million people will die from can-cer worldwide in 2015 and 11.4 million will die in 2030. More than 70% of all cancer deaths occur in low and middle income countries. These statistics underlie the fact that cancer is the deadliest of all human diseases. The enormity of the glo-bal healthcare costs as a result of cancer cannot be overemphasized.

This seventh volume in the series, Methods of Cancer Diagnosis, Therapy, and Prognosis, presents an overview of the molecular basis of cancer, cancer biomarkers, tumor angiogenesis, use of imaging techniques for cancer diagnosis, treatments using chemotherapy, radiation, radioimmunotherapy, and monoclonal antibodies. Part I presents an overview of the pharmacogenomics into cancer therapy, cancer stem cells, and translation of in vitro cell lines results into clinical practice.

In Part II, head and neck cancer is dis-cussed. The global number of annual new cases of this malignancy is ~500,000. These malignancies include oral squamous cell carcinoma, salivary gland tumors, tonsil-lar cancer, tongue cancer, nasopharyngeal carcinoma, and retinoblastoma, which are detailed. In Part III, diagnosis, therapy, and prognosis of thyroid carcinoma are dis-cussed. The global number of new cases of thyroid cancer is ~141,000, and the number of worldwide thyroid mortalities is ~35,375. The number of new cases of this cancer in the United States is ~33,550. Molecular genetics of thyroid cancer, gene expres-sion markers for diagnosis, papillary thy-roid carcinoma diagnosis, and use of PET imaging for diagnosing thyroid cancer are detailed. Detection of metastasized medul-lary thyroid carcinoma using radiolabeled gastrin analogs is included. Prognosis and treatment of medullary thyroid carcinoma based on stage and age are included.

As in the previous six volumes of this series, each chapter is written by distin-guished, practicing clinicians/surgeons/pathologists who provide detailed method-ologies for diagnosis and treatment of the two types of cancer. The volume is divided into three major parts, with each of the two

xv

types of cancers further subdivided into diagnosis, therapy, and prognosis. This volume was written by 89 oncologists representing 16 countries. Their practical experience highlights their writings, which should build and further the endeavors of the readers in this important field. It is my hope that the current volume will join the preceding volumes in this series in form-ing a more complete understanding of globally relevant cancer syndromes. There exists a tremendous public demand on the scientific community to address can-cer prevention, diagnosis, treatment, and, hopefully, cures.

I am grateful to the contributors for their promptness in accepting my suggestions, and I respect their dedication and diligent work in sharing their invaluable knowl-

edge with the public through this series. Each chapter provides unique individual, practical knowledge based on the expertise and knowledge of the authors. The chap-ters contain the most up-to-date practical and theoretical information, and I hope that these volumes will assist the practic-ing readers in their clinical work.

I am thankful to Dr. Dawood Farahi and Dr. Kristie Reilly for recognizing the importance of scholarship (research, writing, and publishing) in an institu-tion of higher learning and for providing the resources for completing this project. I appreciate receiving expert help from Myrna Ortiz and Erin McNally in prepar-ing this volume.

M.A. Hayat March 2009

xvi Preface

Contents of Volumes 1, 2, 3, 4, 5 and 6

Volume 1

1. Breast Cancer: An Introduction

2. Breast Cancer: Computer-Aided Detection

3. Sebaceous Carcinoma of the Breast: Clinicopathologic Features

4. Breast Cancer: Detection by In-Vivo Imaging of Angiogenesis

5. Breast and Prostate Biopsies: Use of Optimized High-Throughput MicroRNA Expression for Diagnosis (Methodology)

6. Familial Breast Cancer: Detection of Prevalent High-Risk Epithelial Lesions

7. Differentiation Between Benign and Malignant Papillary Lesions of Breast: Excisional Biopsy or Stereotactic Vacuum-Assisted Biopsy (Methodology)

8. Multicentric Breast Cancer: Sentinel Node Biopsy as a Diagnostic Tool

9. Breast Cancer Recurrence: Role of Serum Tumor Markers CEA and CA 15-3

10. Breast Cancer Patients Before, During or After Treatment: Circulating Tumor Cells in Peripheral Blood Detected by Multigene Real-Time Reverse Transcriptase-Polymerase Chain Reaction

11. Breast Cancer Patients: Diagnostic Epigenetic Markers in Blood

xvii

xviii Contents of Volumes 1, 2, 3, 4, 5 and 6

12. Breast Cancer Patients: Detection of Circulating Cancer Cell-Related mRNA Markers with Membrane Array Method

13. Prediction of Metastasis and Recurrence of Breast Carcinoma: Detection of Survivin-Expressing Circulating Cancer Cells

14. Node-Negative Breast Cancer: Predictive and Prognostic Value of Peripheral Blood Cytokeratin-19 mRNA-Positive Cells

15. Breast and Colon Carcinomas: Detection with Plasma CRIPTO-1

16. Breast Cancer Risk in Women with Abnormal Cytology in Nipple Aspirate Fluid

17. Tissue Microarrays: Construction and Utilization for Biomarker Studies

18. Systematic Validation of Breast Cancer Biomarkers Using Tissue Microarrays: From Construction to Image Analysis

19. Phyllodes Tumors of the Breast: The Role of Immunohistochemistry in Diagnosis

20. Phyllodes Tumor of the Breast: Prognostic Assessment Using Immunohistochemistry

21. Metaplastic Breast Carcinoma: Detection Using Histology and Immunohistochemistry

22. Invasive Breast Cancer: Overexpression of HER-2 Determined by Immunohistochemistry and Multiplex Ligation-Dependent Probe Amplifi cation

23. Operable Breast Cancer: Neoadjuvant Treatment (Methodology)

24. Chemotherapy for Breast Cancer

25. Locally Advanced Breast Cancer: Role of Chemotherapy in Improving Prognosis

26. Relevance of Dose-Intensity for Adjuvant Treatment of Breast Cancer

Contents of Volumes 1, 2, 3, 4, 5 and 6 xix

27. Advanced Breast Cancer: Treatment with Docetaxel/Epirubicin

28. Systemic Therapy for Breast Cancer: Using Toxicity Data to Inform Decisions

29. Chemotherapy for Metastatic Breast Cancer Patients Who Received Adjuvant Anthracyclines (An Overview)

30. Estrogen Receptor-Negative and HER-2/neu-Positive Locally Advanced Breast Carcinoma: Therapy with Paclitaxel and Granulocyte-Colony Stimulating Factor

31. Breast Cancer: Side Effects of Tamoxifen and Anastrozole

32. Breast Cancer: Expression of HER-2 and Epidermal Growth Factor Receptor as Clinical Markers for Response to Targeted Therapy

33. Young Breast Cancer Patients Undergoing Breast-Conserving Therapy: Role of BRCA1 and BRCA2

34. Radiation Therapy for Older Women with Early Breast Cancer

35. Acute Side Effects of Radiotherapy in Breast Cancer Patients: Role of DNA-Repair and Cell Cycle Control Genes

36. 18F-Fluorodeoxyglucose/Positron Emission Tomography in Primary Breast Cancer: Factors Responsible for False-Negative Results

37. Sentinel Lymph Node Surgery During Prophylactic Mastectomy (Methodology)

38. Breast Conservation Surgery: Methods

39. Lymph Node-Negative Breast Carcinoma: Assessment of HER-2/neu Gene Status as Prognostic Value

40. Multifocal or Multicentric Breast Cancer: Understanding Its Impact on Management and Treatment Outcomes

41. Are Breast Cancer Survivors at Risk for Developing Other Cancers?

xx Contents of Volumes 1, 2, 3, 4, 5 and 6

42. Distant Metastasis in Elderly Patients with Breast Cancer: Prognosis with Nodal Status

43. Concomitant Use of Tamoxifen with Radiotherapy Enhances Subcutaneous Breast Fibrosis in Hypersensitive Patients

44. Malignant Phyllodes Tumor of the Breast: Is Adjuvant Radiotherapy Necessary?

45. Locally Advanced Breast Cancer: Multidrug Resistance

46. Breast Cancer: Diagnosis of Recurrence Using 18 F-Fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography

47. Role of Sentinel Lymph Node Biopsy in Ductal Carcinoma In Situ: Diagnosis and Methodology

48. Breast Conservation Treatment of Early Stage Breast Carcinoma: Risk of Cardiac Mortality

Volume 2

Part I General Methods and Overviews

1. Metabolic Transformations of Malignant Cells: An Overview

2. Detection of Recurrent Cancer by Radiological Imaging

3. Tumor Gene Therapy: Magnetic Resonance Imaging and Magnetic Resonance Spectroscopy

4. Assessment of Gene Transfer: Magnetic Resonance Imaging and Nuclear Medicine Techniques

5. Role of Mutations in TP53 in Cancer (An Overview)

6. Personalized Medicine for Cancer

7. Radiation Doses to Patients Using Computed Radiography, Direct Digital Radiography and Screen-Film Radiography

Contents of Volumes 1, 2, 3, 4, 5 and 6 xxi

8. Cancer Vaccines and Immune Monitoring (An Overview)

9. New Insights into the Role of Infection, Immunity, and Apoptosis in the Genesis of the Cancer Stem Cell

10. Successful Cancer Treatment: Eradication of Cancer Stem Cells

11. Overexposure of Patients to Ionizing Radiation: An Overview

Part II Lung Cancer

12. Lung Carcinoma

13. Extra-Pulmonary Small Cell Cancer: Diagnosis, Treatment, and Prognosis

14. Magnetic Resonance Imaging of the Lung: Automated Segmentation Methods

15. Peripheral Lung Lesions: Diagnosis Using Transcutaneous Contrast-Enhanced Sonography

16. Small Pulmonary Nodules: Detection Using Multidetector-Row Computed Tomography

17. Secondary Primary Cancer Following Chemoradiation for Non-Small-Cell Lung Cancer

18. Advanced Non-Small Cell Lung Cancer: Second-Line Treatment with Docetaxel

19. Non-Small Cell Lung Cancer with Brain Metastases: Platinum-Based Chemotherapy

20. Non-Small Cell Lung Carcinoma: EGFR Gene Mutations and Response to Gefi tinib

21. Advanced Non-Small Cell Lung Carcinoma: Acquired Resistance to Gefi tinib

22. Prognostic Signifi cance of [18F]-Fluorodeoxyglucose Uptake on Positron Emission Tomography in Patients with Pathological Stage I Lung Adenocarcinoma

xxii Contents of Volumes 1, 2, 3, 4, 5 and 6

23. Non-Small Cell Lung Cancer: Prognosis Using the TNM Staging System

24. Differentiation Between Malignant and Benign Pleural Effusions: Methylation Specifi c Polymerase Chain Reaction Analysis

25. Pathological Distinction of Pulmonary Large Cell Neuroendocrine Carcinoma from Small-Cell Lung Carcinoma Using Immunohistochemistry

26. Differentiating Between Pleuropulmonary Desmoid Tumors and Solitary Fibrous Tumors: Role of Histology and Immunohistochemistry

27. Non-Small Cell Lung Cancer with Brain Metastasis: Role of Epidermal Growth Factor Receptor Gene Mutation

Part III Prostate Cancer

28. Prostate Carcinoma

29. The Role of Intermediary Metabolism and Molecular Genetics in Prostate Cancer

30. Array-Based Comparative Genomic Hybridization in Prostate Cancer: Research and Clinical Applications

31. Prostate Cancer: Role of Vav3 Overexpression in Development and Progression

32. Prostate Cancer: Detection and Monitoring Using Mitochondrial Mutations as a Biomarker

33. Prognostic Markers in Prostate Carcinoma

34. Prostate Cancer: Detection of Free Tumor-Specifi c DNA in Blood and Bone Marrow

35. Prostate Carcinoma: Evaluation Using Transrectal Sonography

36. Prostate Cancer: 16b-[18F]Fluoro-5α-Dihydrotesterone(FDHT) Whole-Body Positron Emission Tomography

37. Effects of Standard Treatments on the Immune Response to Prostate Cancer

Contents of Volumes 1, 2, 3, 4, 5 and 6 xxiii

38. Vinorelbine, Doxorubicin, and Prednisone in Hormone Refractory Prostate Cancer

39. Locally Advanced Prostate Cancer Biochemical Recurrence After Radiotherapy: Use of Cyclic Androgen Withdrawal Therapy

Volume 3

Part I Gastrointestinal Cancers

1. Introduction: Gastrointestinal Cancer

2. Metastatic Gastrointestinal Cancer: Safety of Cisplatin Combined with Continuous 5-FU Versus Bolus 5-FU and Leucovorin (Methodology)

3. Gastrointestinal Cancer: Endoscopic Submucosal Dissection (Methodology)

4. Gastrointestinal Epithelial Neoplasms: Endoscopic Submucosal Dissection (Methodology)

5. Inoperable Abdomino-Pelvic Tumors: Treatment with Radio-Frequency Ablation and Surgical Debulking

6. Gastrointestinal Neuroendocrine Tumors: Diagnosis Using Gastrin Receptor Scintigraphy

Part II Esophageal Cancer

7. Distal Esophagus: Evaluation with 18F-FDG PET/CT Fusion Imaging

8. Endoscopic Ultrasound and Staging of Esophageal Cancer

9. Esophageal Cancer: Role of RNASEN Protein and microRNA in Prognosis

10. Esophageal Cancer: Initial Staging

xxiv Contents of Volumes 1, 2, 3, 4, 5 and 6

Part III Gastric Cancer

11. Automated Disease Classifi cation of Colon and Gastric Histological Samples Based on Digital Microscopy and Advanced Image Analysis

12. Early Gastric Cancer: Prediction of Metachronous Recurrence Using Endoscopic Submucosal Dissection (Methodology)

13. Helicobacter pylori-Infected Neoplastic Gastric Epithelium: Expression of MUC2 as a Biomarker

14. Gastric Cancer: Role of Intestinal Metaplasia by Histochemical Detection Using Biopsy Specimens

15. Gastric Cancer: Antitumor Activity of RUNX3

16. Early Gastric Cancer: Laparoscopic Gastrectomy (Methodology)

17. Gastric Cancer: Overexpression of Hypoxia-Inducible Factor 1 as a Prognostic Factor

Part IV Pancreatic Cancer

18. Pancreatic Cancer: Hepatoma-Derived Growth Factor as a Prognostic Factor

19. Pancreatic Cancer: 18F-Fluorodeoxyglucose Positron Emission Tomography as a Prognostic Parameter

20. Imaging and Pathologic Findings of Peculiar Histologic Variants of Pancreatic Endocrine Tumors

21. Periampullary Adenocarcinoma: Diagnosis and Survival After Pancreaticoduodenectomy

22. Unresectable Locally Advanced Pancreatic Cancer: Concurrent Chemotherapy

Index

Contents of Volumes 1, 2, 3, 4, 5 and 6 xxv

Volume 4

Part I Colorectal Cancer

1. Introduction: Colorectal Cancer

2. Poorly Differentiated Colorectal Adenocarcinoma: (Methodology)

3. Colorectal Cancer: Immunohistochemical Diagnosis with Heterogenous Nuclear Ribonucleoprotein K

4. Metastases and Recurrence of Colorectal Cancer: Diagnostic Role of Immunoscintigraphy

5. Colorectal Cancer Diagnosis Using DNA Levels in Blood and Stool

6. Colorectal Carcinoma: Identifi cation of MicroRNAs Using Real-Time Polymerase Chain Reaction

7. Colorectal Cancer: Optimization of the Combination of 5-Flouroracil and Irinotecan

8. Detection of Abdominal Abscesses After Colorectal Surgery: Ultrasonography, Computed Tomography, and Gallium Scan

9. Antimetastatic Therapy in Colorectal Cancer: Role of Tumor Cell Matrix Metalloproteinase 9 (Methodology)

10. Endoscopic Resection of Early Colorectal Tumours: Novel Diagnostic and Therapeutic Techniques

11. Role of Stromal Variables in Development and Progression of Colorectal Cancer

12. Quantitative Assessment of Colorectal Cancer Perfusion: Perfusion Computed Tomography and Dynamic Contrast-Enhanced Magnetic Resonance Imaging

13. Colorectal Cancer: Positron Emission Tomography

14. Prognostic Signifi cance of Protein Markers in Colorectal Cancer Stratifi ed by Mismatch Repair Status

15. Colorectal Cancer: Lactate Dehydrogenase (LDH) Activity as a Prognostic Marker

xxvi Contents of Volumes 1, 2, 3, 4, 5 and 6

Part II Colon Cancer

16. Detection of Tumor Cells in Lymph Nodes of Colon Cancer Patients Using Real-Time Quantitative Reverse Transcription-Polymerase Chain Reaction

17. Colon Cancer: Laparoscopic Surgery

18. Sentinal Node-Based Immunotherapy of Colon Cancer

Part III Rectal Cancer

19. Rectal Cancer: Preoperative Staging Using Endorectal Ultrasonography (Methodology)

20. Rectal Cancer: Spectral Imaging and Immunohistochemistry of Thymidylate Synthase

21. Cancer of the Rectum: Abdominoperineal and Sphincter-Saving Resections

22. Chemoradiation for Rectal Cancer

23. Resectable Rectal Cancer: Preoperative Short-Course Radiation

24. Preoperative Chemoradiotherapy Allows for Local Control in Rectal Cancer, but Distant Metastases Remain an Unsolved Problem

25. Locally Advanced Rectal Cancer: Combined Chemotherapy During Preoperative Radiation Therapy

Part IV Colorectal Liver Metastases

26. Colorectal Cancer Liver Metastases: Neoadjuvant Therapy with Bevacizumab

27. Colorectal Liver Metastases: Radiofrequency Ablation

Part V Anal Cancer

28. Anal Squamous Cell Carcinomas: Diagnosis Using p63 Immunohistochemistry

29. Anorectal Melanoma: Prediction of Outcome Based on Molecular and Clinicopathologic Features

Contents of Volumes 1, 2, 3, 4, 5 and 6 xxvii

Volume 5

Part I Liver Cancer

A. Diagnosis

1. Applications of Positron Emission Tomography in Liver Imaging: An Overview

2. Localized Fibrous Tumor of the Liver: Imaging Features

3. A Radial Magnetic Resonance Imaging Method for Imaging Abdominal Neoplasms

4. Liver: Helical Computed Tomography and Magnetic Resonance Imaging

Part II Resectable Liver Cancer

A. Diagnosis

5. Selection of Patients for Resection of Hepatic Colorectal Metastases: 18F-Fluorodeoxyglucose/Positron Emission Tomography

B. Treatment

6. Ultrasonography During Liver Surgery

Part III Unresectable Liver Cancer

A. Treatment

7. Intraoperative Magnetic Resonance Imaging for Radiofrequency Ablation of Hepatic Tumors

8. Surgically Unresectable and Chemotherapy-Refractory Metastatic Liver Carcinoma: Treatment with Yttrium-90 Microsphere Followed by Assessment with Positron Emission Tomography

B. Prognosis

9. Unresectable Liver Metastases from Colorectal Cancer: Methodology and Prognosis with Radiofrequency Ablation

xxviii Contents of Volumes 1, 2, 3, 4, 5 and 6

Part IV Hepatocellular Carcinoma

A. Diagnosis

10. Screening with Ultrasonography of Patients at High-Risk for Hepatocellular Carcinoma: Thrombocytopenia as a Valid Surrogate of Cirrhosis

11. Hepatocellular Carcinoma: Contrast-Enhanced Sonography

12. Focal Liver Lesion: Nonlinear Contrast-Enhanced Ultrasound Imaging

13. Hepatocellular Carcinoma: Magnetic Resonance Imaging

14. Expression of Vascular Endothelial Growth Factor in Hepatocellular Carcinoma: Correlation with Radiologic Findings

15. Detection of Small Hepatic Lesions: Superparamagnetic Oxide-Enhanced Diffusion-Weighted T2 FSE Imaging

16. Diagnosis of Hepatocellular Carcinoma: Multidetector-Row Computed Tomography and Magnetic Resonance Imaging

17. Hepatocellular Carcinoma: Effect of Injection Rate/Injection Duration of Contrast Material on Computed Tomography

18. Detection of Combined Hepatocellular and Cholangiocarcinomas: Enhanced Computed Tomography

19. Hepatocellular Carcinoma and Adenomatous Hyperplasia (Dysplastic Nodules): Dynamic Computed Tomography and a Combination of Computed Tomography and Angiography

20. Hepatocellular Cancer in Cirrhotic Patients: Radiological Imaging

B. Treatment

21. Treatment of Hepatocellular Carcinoma with Thalidomide: Assessment with Power Doppler Ultrasound

22. Perfusion Scintigraphy with Integrated Single Photon Emission Computed Tomography/Computed Tomography in the Management of Transarterial Treatment of Hepatic Malignancies

23. Postoperative Interferon Alpha Treatment of Patients with Hepatocellular Carcinoma: Expression of p48 Using Tissue Microarray

Contents of Volumes 1, 2, 3, 4, 5 and 6 xxix

C. Prognosis

24. Hepatocellular Carcinoma: Overexpression of Homeoprotein Six 1 as a Marker for Predicting Survival

25. Hepatocellular Carcinoma: KiSS-1 Overexpression as a Prognostic Factor

26. Hepatocellular Carcinoma: Prognosis Using Hepatoma-Derived Growth Factor Immunohistochemistry

27. Hepatitis C Virus-Related Human Hepatocellular Carcinoma: Predictive Markers Using Proteomic Analysis (Methodology)

Part V Metastases

A. Diagnosis

28. Liver Metastases from Colorectal Cancer: Ultrasound Imaging

29. Preclinical Liver Metastases: Three-Dimensional High-Frequency Ultrasound Imaging

30. Colorectal Liver Metastases: 18F-Fluorodeoxyglucose-Positron Emission Tomography

Part VI Biliary Cancer

A. Diagnosis

31. Biliary Cystic Tumors: Clinicopathological Features

32. Cholangiocarcinoma: Intraductal Sonography

B. Prognosis

33. Extrahepatic Bile Duct Carcinoma: Role of the p53 Protein Family

34. Extrahepatic Bile Duct Carcinoma: Mucin 4, a Poor Prognostic Factor

C. Treatment

35. Hilar Cholangiocarcinoma: Photodynamic Therapy and Stenting

xxx Contents of Volumes 1, 2, 3, 4, 5 and 6

Part VII Splenic Cancer

A. Diagnosis

36. Splenic Metastases: Diagnostic Methods

Volume 6

Part I Ovarian Cancer

A. Diagnosis

1. Identifi cation of Biomarkers for Clear Cell Ovarian Adenocarcinoma

2. Ovarian Carcinoma: Diagnostic Immuno-histochemistry of MUCIN4 (MUC4)

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

4. Subgroups of Ovarian Carinoma: Identifi cation Using Differential Gene Expression

5. Sertoliform Endometrioid Carcinoma of the Ovary: Diagnosis and Prognosis

B. Prognosis

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

7. Clear Cell Carcinoma of the Ovary: Prognosis Using Cytoreductive Surgery

8. Advanced Ovarian Cancer: Prediction of Surgical Outcomes Using Computed Tomography

Part II Renal Cancer

A. Treatment

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

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

11. Renal Cell Carcinoma: Preoperative Treatment with Cytokines Followed by Surgery

Contents of Volumes 1, 2, 3, 4, 5 and 6 xxxi

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

13. Wilms Tumor: Prognosis Using Microvessel Density

Part III Urogenitary Tract Cancer

A.Adrenal

14. Adenomatoid Tumor of the Adrenal Gland: Differential Diagnosis Using Immunohistochemistry

15. Testicular Cancer: Post-Chemotherapy Retroperitoneal Lymph Node Dissection

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

Part IV Urinary Bladder Cancer

Diagnosis

17. Urothelial Bladder Cancer: Screening with Urine-Based Tumor Markers

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

Part V Cervical Uterine Cancer

Diagnosis

19. Uterine Cervical Glandular Lesions: Differentiation Using Immunohistochemistry of Mucins

20. Uterine Cervical Carcinoma: Preoperative Magnetic Resonance Imaging Staging

Treatment

21. Cancer Imaging and Intracavitary Brachytherapy for Cervical Cancer

22. Cervical Cancer: Methods for Assessing the Quality of Life

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

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

xxxii Contents of Volumes 1, 2, 3, 4, 5 and 6

Part VI Skin Cancer

Melanoma

25. Neurofi bromatosis Type 1-Associated Malignant Melanoma: Molecular Evidence of Inactivation of the NF1 Gene

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

27. Malignant Melanoma Versus Deep Penetrating Nevus: Diagnostic and Prognostic Immuno-Histochemistry of Dipeptidyl Peptidase IV (Methodology)

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

Part VII Leukemia

29. Pretreated Chronic Lymphocytic Leukemia: Use of Alemtuzumab

Part VIII Multiple Myeloma

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

Part IX Sarcoma

Diagnosis

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

32. Synovial Sarcoma: Role of TLE1 as a Diagnostic mmunohistochemical Marker

33. The Immunohistochemistry of Kaposi’s Sarcoma

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

Treatment

35. Sarcoma: Treatment with Ecteinascidin-743

xxxiii

Contributors ........................................................................................................... vii

Preface ..................................................................................................................... xv

Contents of Volumes 1, 2, 3, 4, 5 and 6 ................................................................ xvii

Part I General Methods And Overviews

Diagnosis

1. Role of RNA Interference in Understanding the Molecular Basis of Cancer ................................................................................................ 5Jeffrey P. MacKeigan and L. Alex Gaither

Mechanism of RNA Interference .................................................................. 5RNAI as a Cell Based Screening Tool .......................................................... 7RNAI to Understand Compound Mechanism of Action ............................... 10Compound Sensitization, Combination Strategies and Synthetic

Lethal RNAI Screens ............................................................................... 13Problems Associated with RNAI Based Approaches ................................... 16

References ......................................................................................................... 18

2. Cancer Biomarkers (An Overview) ............................................................... 21William C.S. Cho

Introduction ................................................................................................... 21Emerging Technologies for Cancer Biomarker Discovery ........................... 21

DNA Microarray ....................................................................................... 22Serial Analysis of Gene Expression .......................................................... 23MicroRNA Microarray ............................................................................. 23

Contents

xxxiv Contents

Two Dimensional Polyacrylamide Gel Electrophoresis ........................... 23Free Flow Electrophoresis ........................................................................ 23Capillary Electrophoresis .......................................................................... 24Matrix-Assisted Laser Desorption/Ionization Time-of-Flight

Mass Spectrometry ................................................................................ 24Surface-Enhanced Laser Desorption/Ionization Time-of-Flight

Mass Spectrometry ................................................................................ 25Liquid Chromatography Coupled with Tandem

Mass Spectrometry ................................................................................ 25Linear Ion Trap Quadrupole-Orbitrap ....................................................... 25Imaging Mass Spectrometry ..................................................................... 26Isotope-Coded Affi nity Tags ..................................................................... 26Multiple Reaction Monitoring .................................................................. 26Absolute Quantifi cation of Proteins .......................................................... 27Protein Microarray .................................................................................... 27Tissue Array .............................................................................................. 27Bioinformatics ........................................................................................... 28

Currently Used Cancer Biomarkers (Table 2.2) ............................................ 28Biomarkers for the Diagnosis of Cancers (Table 2.3) ................................... 30

Genomic-Based Biomarkers in Cancer ..................................................... 30Transcriptomic-Based Biomarkers in Cancer ........................................... 31Proteomic-Based Biomarkers in Cancer ................................................... 31

Biomarkers for the Treatment and Progression of Cancers (Table 2.3) ................................................................................................. 32Genomic-Based Biomarkers in Cancer ..................................................... 32Transcriptomic-Based Biomarkers in Cancer ........................................... 32Proteomic-Based Biomarkers in Cancer ................................................... 33

Biomarkers for the Prognosis of Cancers (Table 2.3) ................................... 33Genomic-Based Biomarkers in Cancer ..................................................... 33Transcriptomic-Based Biomarkers in Cancer ........................................... 34Proteomic-Based Biomarkers in Cancer ................................................... 34

Challenges and Perspectives ......................................................................... 35References ......................................................................................................... 36

3. Tumor Angiogenesis in Cancers: Expression of CD105 Marker ................ 41Osamu Tokunaga, Rahmawati Minhajat, and Daisuke Mori

Introduction ................................................................................................... 41Morphological Features of Tumor Angiogenesis ......................................... 41Detection of the Endothelium by Immunohistology ..................................... 43

Antigenecity Retrieval .............................................................................. 43Immunohistology ...................................................................................... 43

Simultaneous Mass and Comparative Study: Tissue Array .......................... 44Specifi c Markers for Vascular Endothelium in Tumor ................................. 44

Angiogenesis ............................................................................................. 44CD105/Endoglin Endothelial Marker Specifi c for Newly

Formed Blood Vessels ............................................................................... 45CD105 and Vasculogenesis ........................................................................... 45Organ Specifi city of CD105 Positive Tumor Angiogenesis ......................... 46Application of CD105 for Anti-angiogenic Cancer Therapy ....................... 46

References ......................................................................................................... 48

4 Spindle Cell Oncocytoma of the Adenohypophysis: Integrated Clinicopathologic Diagnosis by Imaging, Histology, and Immunohistochemistry ........................................................................... 51I. Vajtai and R. Sahli

Introduction ................................................................................................... 51Clinical Presentation ..................................................................................... 51Imaging Aspects ............................................................................................ 52Histology and Immunophenotype ................................................................. 52Differential Diagnosis ................................................................................... 54Therapeutic and Prognostic Implications ....................................................... 55Discussion and Perspectives ......................................................................... 56

References ......................................................................................................... 56

5. Disseminated Carcinoma of Unknown Primary Site: Detection with F-Fluorodeoxyglucose-Positron Emission Tomography .................................................................................... 59Pascal Sève and John R. Mackey

Introduction ................................................................................................... 59Material and Methods ................................................................................... 60Results ........................................................................................................... 62Discussion ..................................................................................................... 65

References ......................................................................................................... 69

6. Unknown Lymphadenopathy: Diagnosing Using an Endoscopic Ultrasound-Guided Fine-Needle Aspiration Biopsy .................................... 73Ichiro. Yasuda

Introduction ................................................................................................... 73Application .................................................................................................... 73Equipment ..................................................................................................... 73

Echoendoscopes and Endoscopic Ultrasound Processors ......................... 73Needles ...................................................................................................... 74

Procedure ...................................................................................................... 75Preparations ............................................................................................... 75Fine Needle Apiration Biopsy .................................................................. 75Treatment of Sampled Material ................................................................ 75

Contents xxxv

xxxvi Contents

Management After the Procedure ............................................................. 77Diagnostic Yield ............................................................................................ 77

Complications ........................................................................................... 78References ......................................................................................................... 78

Therapy

7. Pretargeted Radioimmunotherapy in Cancer: An Overview ..................... 81Stefano Papi, Chiara Maria Grana, Mirco Bartolomei, Laura Ravasi, Marta Cremonesi, Mahila Ferrari, Luigi Martano, Lucia Garaboldi, Marco Chinol, and Giovanni Paganelli

Introduction ................................................................................................... 81Therapeutic Radioisotopes ............................................................................ 82Limitations of Classical Radioimmunotherapy

in Solid Tumours ....................................................................................... 84Pre-targeting Approach ................................................................................. 85Avidin–Biotin System ................................................................................... 87

Avidin–Biotin Pretargeting in Glioma ...................................................... 89Other Developments ..................................................................................... 95Conclusion .................................................................................................... 96

References ......................................................................................................... 96

8. Chemotherapy-Induced Neurotoxicity ......................................................... 99Susanna B. Park and Matthew C. Kiernan

Abbreviations ................................................................................................ 99Introduction ................................................................................................... 99Clinical Presentations of Neurotoxicity ........................................................ 100Incidence of Neurotoxicity ........................................................................... 101Pathophysiology of Neurotoxicity ................................................................ 101Clinical Evaluation and Assessment ............................................................. 102Neurophysiological Assessment ................................................................... 103Characteristics of Neurotoxic Chemotherapies ............................................ 105

Taxanes...................................................................................................... 105Cisplatin .................................................................................................... 106Vinca Alkaloids ......................................................................................... 107Other Neurotoxic Chemotherapies ........................................................... 107

Oxaliplatin-Induced Neurotoxicity ............................................................... 108Pathophysiological Mechanisms of Oxaliplatin Neuropathy.................... 110Assessment of Oxaliplatin-Induced Neurotoxicity ................................... 110Nerve Excitability Studies in Oxaliplatin-Induced

Neuropathy ............................................................................................ 112Future Directions and Neuroprotection .................................................... 115

References ......................................................................................................... 117

Contents xxxvii

9. Multidrug Resistance ...................................................................................... 121Ernesto Yagüe and Selina Raguz

Infl uence of Pharmacological and Physiological Factors ............................. 121Molecular Mechanisms of Resistance to Traditional Chemotherapy ........... 122

Intracellular Drug Activation .................................................................... 122Detoxifying Systems ................................................................................. 122DNA Repair .............................................................................................. 122Cell Death Regulation ............................................................................... 123Membrane Proteins ................................................................................... 123

Cellular Models to Study Drug Resistance ................................................... 123Leukemic K562 Cells as a Model to Study Multi-drug Resistance .......... 125Bodipy-taxol effl ux assay ......................................................................... 127

Animal Models to Study Drug Resistance .................................................... 128Cancer Stem Cells and Drug Resistance ....................................................... 129Drug Resistance in the Clinic ....................................................................... 129Reversal of Drug Resistance in the Clinical Setting ..................................... 130

References ......................................................................................................... 131

10. Role of Antibodies in Cancer Treatment (An Overview) ............................................................................................... 135Huguette AlbrechtIntroduction ................................................................................................... 135Structure of an Antibody ............................................................................... 135Recombinant Antibodies ............................................................................... 137

Chimeric and Humanized Monoclonal Antibodies ................................... 137Human Monoclonal Antibodies ................................................................ 137Antibody Fragments .................................................................................. 137Antibody Fragments Combinatorial Libraries .......................................... 137

Pharmacokinetics of Antibodies ................................................................... 138Tumor Antigens ............................................................................................ 139Manufacturing of Therapeutic Monoclonal Antibodies ............................... 139Mechanisms of Action of Therapeutic Monoclonal Antibodies

(Pharmacodynamics) ................................................................................. 140Toxicities Associated with Therapeutic Monoclonal Antibodies ................. 143Therapeutic Monoclonal Antibodies Currently Licensed ............................. 143

Anti-CD20 Monoclonal Antibodies .......................................................... 144Anti-CD33 Monoclonal Antibody ............................................................ 145Anti-CD52 Monoclonal Antibody ............................................................ 145Anti-HER-2 Monoclonal Antibody .......................................................... 145Anti-EGFR Monoclonal Antibodies ......................................................... 146Anti-VEGF Monoclonal Antibody ........................................................... 147

Therapeutic Monoclonal Antibodies and Antibody Targeted Therapeutics Under Investigation ............................................................. 148

Clinical Evaluation .................................................................................... 148Preclinical Evaluation ............................................................................... 149

References ......................................................................................................... 150

11. Incorporating Pharmacogenomics into Cancer Therapy ......................... 153Wooin Lee and A. Craig LockhartIntroduction ................................................................................................... 153Current Use of Pharmacogenomics in Clinical Oncology ............................ 154

Thiopurine Methyltransferase (TPMT) ..................................................... 154UDP-Glucuronosyltransferase 1A1 (UGT1A1) ....................................... 155Other Pharmacogenomic Markers in Clinical Investigation ..................... 157

Methodology ................................................................................................. 162Genotyping Assays ................................................................................... 162Different Approaches in Pharmacogenomics ........................................... 163

Implementation of Pharmacogenomics in Drug Discovery and Development ...................................................................................... 165Early Stage Clinical Development (Phase I and II Clinical Trials) .......... 165Late-Stage Clinical Development (Phase III Clinical Trials) ................... 167Incorporating Pharmacogenomics into Clinical Trials:

Technical and Legal Issues ................................................................... 168Future Directions .......................................................................................... 169

References ......................................................................................................... 169

12. Cancer Stem Cells: An Overview ................................................................ 173Eiichi Morii and Katsuyuki AozasaIntroduction ................................................................................................... 173Cancer Stem Cells: Concept ......................................................................... 173Isolation of Cancer Stem Cells ..................................................................... 174Origin of Cancer Stem Cells ......................................................................... 175Epigenetics and Cancer Stem Cells .............................................................. 177Future Perspectives ....................................................................................... 178

References ......................................................................................................... 180

13. Translating In Vitro Cell Lines Result into Clinical Practice ................... 183Jai Prakash Mehta, Lorraine O’Driscoll, Niall Barron, Martin Clynes, and Padraig DoolanIntroduction ................................................................................................... 183How Cell Lines Are Generated ..................................................................... 184Types of Cell Culture .................................................................................... 184Selection Bias ................................................................................................ 184Selection Pressure ......................................................................................... 185Cell Line Preference and Availability ........................................................... 186Cross-Contamination .................................................................................... 187Microbial Contamination .............................................................................. 187

xxxviii Contents

Handling Errors ............................................................................................. 188New Insights: Microarray Gene-Expression Profi ling of Tumours

and Cell Lines ........................................................................................... 188Conclusions ................................................................................................... 189

References ......................................................................................................... 190

Prognosis

14. Classifi cation of Cancer Stage Using Patient’s Immune System .............. 195P. Pellegrini, I. Contasta, A.M. Berghella, T. Del Beato, and D. AdornoIntroduction ................................................................................................... 195Classifi cation System for Cancer Stage ........................................................ 195TH1/TH2/TH3/TH17 Cytokine Physiological Network

in Peripheral Blood Samples ..................................................................... 196TH1/TH2/TH3/HT17 Cytokine Network: Immuno System ..................... 196

Method to Study the TH1/TH2/TH3/HT17 Cytokine Network ................... 198Immune System Through Mathematical Modelling ................................. 199Peripheral Blood Cytokine Network ......................................................... 199

Methods ......................................................................................................... 200Serum Samples .......................................................................................... 200Peripheral Blood Mononuclear Cell Separation and Generation

of Dendritic Cells from Monocytes Using Dynabeads ......................... 200Whole Blood Cell Cultures ....................................................................... 201Cytokine Detection ................................................................................... 201Data Analysis ............................................................................................ 202

Physiological Evaluation of the Immune System ......................................... 203The TH1/TH2/TH3/TH17 Cytokine Network in Healthy Subjects .......... 203Cytokine Network Relationships in Men and Women .............................. 204

How to Defi ne Immunological Parameters for Stage Classifi cation ............. 205Comparative Study with Groups of Healthy Subjects

and Cancer Patients ............................................................................... 205Disease Stage Indices in Colorectal Cancer .................................................. 205

Prognostic Signifi cance of Immunological Parameters ............................ 206Normal Mucosa to Adenoma and Colon Cancer ...................................... 206Accuracy of Prognostic Indices ................................................................ 208Identifying Ranges for Immunological Markers ....................................... 210

References ..................................................................................................... 211

15. Late Relapse of Germ Cell Malignancies: Incidence, Management, and Prognosis ........................................................................ 215Jan Oldenburg and Sophie D. FossaIntroduction ................................................................................................... 215Incidence ....................................................................................................... 215Seminoma Clinical Stage I ............................................................................ 216

Contents xxxix

xl Contents

Seminoma Clinical Stage >I ......................................................................... 217Nonseminoma Clinical Stage I ..................................................................... 218Nonseminoma Clinical Stage >I ................................................................... 219Detection and Differential Diagnosis ............................................................ 220Treatment and Survival ................................................................................. 222

Seminoma ................................................................................................. 224Non-seminoma .......................................................................................... 224

References ......................................................................................................... 225

Part II Head and Neck Cancer

16. Head and Neck Squamous Cell Carcinoma: Therapy with Fusaric Acid/Paclitaxel ......................................................... 229Brendan C. Stack Jr., Brett Clarke, Joshua McElderry, Yeumeng Dai, and Jian-Hui YeIntroduction ................................................................................................... 229A New Class of Agents for Head and Neck Cancer? ................................... 229A New Target in the Head and Neck Cancer Cell? ....................................... 230Evidence for Furaic Acid as a New Head and Neck

Cancer Therapy ......................................................................................... 231References ......................................................................................................... 233

17. Early Stage Oral Squamous Cell Carcinoma: Use of Signal Transducer and Activator of Transcription 3 as a Risk Factor for Poor Diagnosis ............................................................................. 237N.G. Shah and T.I. TrivediIntroduction ................................................................................................... 237Signal Transducers and Activators of Transcription ..................................... 238Activation of Signal Transducers and Activators of Transcription

Signaling ................................................................................................... 239Signal Transducer and Activator of Transcription 3 ..................................... 240Physiological Role of Signal Transducer and Activator

of Transcription 3 ...................................................................................... 240Signal Transducer and Activator of Transcription 3 in Oncogenesis ........... 241Signal Transducer and Activator of Transcription 3 in Oral

Squamous Cell Carcinoma ........................................................................ 241Electrophoretic Mobility Shift Assay ....................................................... 241Competition Mobility Shift Assay ............................................................ 242Super Shift Assay ...................................................................................... 242DNA Binding Affi nity Purifi cation ........................................................... 243In Situ Hybridization ................................................................................. 244Immunoblotting......................................................................................... 245Immunohistochemical Localization .......................................................... 246

Contents xli

Reverse Transcription–Polymerase Chain Reaction ................................. 250References ......................................................................................................... 252

18. Salivary Gland Tumors: Preoperative Tissue Characterization with Apparent Diffusion Coeffi cient Mapping ........................................... 255Takashi Nakamura, Misa Sumi, and MarcVan CauterenIntroduction ................................................................................................... 255Diffusion-Weighted Imaging ........................................................................ 255

Measurement of Diffusion-Weighted Imaging ......................................... 256Clinical Use of Diffusion Weighted Imaging............................................ 258

Salivary Gland Tumors ................................................................................. 2602D ADC Color Mapping of Salivary Gland Tumors ................................ 261ADCs of Healthy Major Salivary Glands ................................................. 263ADCs of Benign Salivary Gland Tumors ................................................. 266ADCs of Malignant Salivary Gland Tumors ............................................. 266

Tissue Characterization with Apparent Diffusion Coeffi cient Mapping ................................................................................. 267

Applications of Apparent Diffusion Coeffi cient Mapping to the Diagnosis of Malignant Lesions ..................................................... 267

High-Resolution Imaging of Malignant Lesions .......................................... 268References ......................................................................................................... 268

19. Role of Human Papillomavirus in Tonsillar Cancer .................................. 271Eva Munck-Wikland, Lalle Hammarstedt, and Hanna DahlstrandIntroduction ................................................................................................... 271Tonsillar Cancer ............................................................................................ 271Human Papillomavirus (HPV) ...................................................................... 271Epidemiology ................................................................................................ 272Evidence of HPV Role in Carcinogenesis .................................................... 273Sexual Behaviour and Oropharyngeal Cancer .............................................. 275HPV and Prognosis in Tonsillar Cancer ....................................................... 275Impact of Viral Load on Prognosis ............................................................... 276P16INK4A – A Surrogate Marker for HPV 16 ................................................. 276HPV in Other Oropharyngeal Cancer ........................................................... 277Future Perspectives ....................................................................................... 277Methods of HPV Detection and Genotyping ................................................ 278

Polymerase Chain Reaction (PCR) ........................................................... 278Hybrid Capture .......................................................................................... 278DNA In Situ Hybridization (ISH) ............................................................. 278HPV Genotyping ....................................................................................... 279HPV mRNA Amplifi cation and Detection ................................................ 279HPV Serology ........................................................................................... 280

xlii Contents

HPV DNA Load ........................................................................................ 280References ......................................................................................................... 281

20. Quantitative Reverse Transcription–Polymerase Chain Reaction Based Assessment of the Candidate Biomarkers for Tongue Cancer Metastasis ...................................................................... 285Xiaofeng Zhou, Tianwei Yu, and David T. WongIntroduction ................................................................................................... 285Quantitative Polymerase Chain Reaction ..................................................... 285

QPCR Chemistries .................................................................................... 286Quantifi cation of Results ........................................................................... 288

Oral Tongue Cancer ...................................................................................... 290Oral Tongue Squamous Cell Carcinoma (OTSCC), A Major

Subset of Oral Cancer ........................................................................... 290Metastasis – A Major Clinical Problem of Oral Cancer ........................... 291

The Quantitative Polymerase Chain Reaction Based Evaluation of Candidate Tongue Cancer Metastasis Markers ..................................... 293Cancer Biomarkers .................................................................................... 293QRT-PCR Based Assessments of CTTN and MMP9

in Tongue Cancer .................................................................................. 294Quantifi cation and Statistical Evaluation of the Markers ......................... 298

Future Developments .................................................................................... 300References ......................................................................................................... 301

21. Nasopharyngeal Carcinoma (Retropharyngeal Lymph Node Metastasis): Spread Pattern, Prognosis, and Staging ...................... 303Li Li and Li-Zhi LiuIntroduction ................................................................................................... 303Materials and Methods .................................................................................. 304

Patient Characteristics ............................................................................... 304Imaging Protocol and Criteria for RLN Metastasis and Other

Cervical Lymph Node ........................................................................... 305Treatment .................................................................................................. 305Follow-Up and Statistical Analysis ........................................................... 306

Results ........................................................................................................... 307Incidence and Distribution of RLNs Demonstrated by MRI .................... 307Relationship Between Metastatic RLNs and Tumor Involvement ............ 307Prognosis and Staging of RLN Metastasis Based on CT Data ................. 308

Discussion ..................................................................................................... 310Imaging Criteria for Metastatic RLNs ...................................................... 310Incidence of RLNs Metastasis .................................................................. 311Spread Patterns of RLNs Metastasis ......................................................... 312Prognostic Signifi cance and Staging of RLNs Metastasis ........................ 313

References ......................................................................................................... 315

Contents xliii

22. Retinoblastoma: Diagnosis, Treatment and Prognosis .............................. 319Aubin Balmer, Francis Munier, and Leonidas ZografosIntroduction ................................................................................................... 319Diagnosis ....................................................................................................... 319

Epidemiology ............................................................................................ 319Genetics ..................................................................................................... 320Semeiology ............................................................................................... 320Clinical Features ....................................................................................... 321Clinical Investigation (Balmer and Munier 2002) .................................... 324Tumor Growth ........................................................................................... 325Second or Multiple Nonocular Tumors .................................................... 326Classifi cation ............................................................................................. 327Differential Diagnosis ............................................................................... 327

Treatment ...................................................................................................... 328Treatment Methods ................................................................................... 329Chemotherapy ........................................................................................... 329Focal Consolidation Treatment ................................................................. 330Future Advances ....................................................................................... 332

Prognosis ....................................................................................................... 333References ......................................................................................................... 334

Part III Thyroid Carcinoma

Diagnosis

23. Molecular Genetics of Thyroid Cancer ....................................................... 341Deanne King, Donald Bodenner, and Brendan C. Stack Jr.Introduction ................................................................................................... 341Papillary ........................................................................................................ 341

RET Oncogene .......................................................................................... 343RAS Oncogene .......................................................................................... 344BRAF ........................................................................................................ 344APC ........................................................................................................... 344

Follicular ....................................................................................................... 345RAS Oncogene .......................................................................................... 345PAX8/PPARg............................................................................................. 345PTEN ......................................................................................................... 345

Medullary ...................................................................................................... 346RET Oncogene .......................................................................................... 346

Anaplastic ..................................................................................................... 347P53 Mutations ........................................................................................... 347MRP-1 ....................................................................................................... 348

Molecular Profi ling ....................................................................................... 348Fine Needle Aspirations (FNA) Reports ....................................................... 348

References ......................................................................................................... 349

xliv Contents

24. Thyroid Cancer: Identifi cation of Gene Expression Markers for Diagnosis .................................................................................................. 353Obi L. Griffi th, Adrienne Melck, Steven J.M. Jones, and Sam M. WisemanIntroduction ................................................................................................... 353Gene Expression Technologies ..................................................................... 354

cDNA Microarrays .................................................................................... 354Oligonucleotide Arrays ............................................................................. 355Serial Analysis of Gene Expression .......................................................... 356Future Tag-Sequence Methods.................................................................. 356

Experimental Issues ...................................................................................... 357Array Design ............................................................................................. 357Sample Preparation ................................................................................... 357Replicates .................................................................................................. 358

Data Analysis Issues ..................................................................................... 358Quality Assessment ................................................................................... 358Normalization and Background Correction .............................................. 359Probe/Tag Mapping ................................................................................... 359Differential Expression Analysis .............................................................. 360Expression Profi ling Software and Databases .......................................... 361

Validation Methods ....................................................................................... 361Clustering and Classifi cation Analysis ......................................................... 363

Cancer Diagnosis Using Tumor Gene Expression Signatures .................. 363Defi ning New Molecular Subtypes with Gene Expression Data .............. 363Developing Biomarkers or Panels from Microarray Class Predictors ...... 364

Expression Profi ling Studies in Thyroid Cancer ........................................... 364Cross-Platform Integration and Meta-Analysis ............................................ 367Molecular Markers for Thyroid Cancer ........................................................ 369References ..................................................................................................... 372

25. Papillary Thyroid Carcinoma: Use of HBME1 and CK19 as Diagnostic Markers .................................................................................. 379M.R. Nasr and S. MukhopadhyayIntroduction ................................................................................................... 379Protocol ......................................................................................................... 380Materials ....................................................................................................... 380Methods ......................................................................................................... 381Interpretation of Staining .............................................................................. 381HBME1 in Papillary Thyroid Carcinoma and Benign

Thyroid Lesions ........................................................................................ 381CK19 in Papillary Thyroid Carcinoma and Benign

Thyroid Lesions ........................................................................................ 383References ..................................................................................................... 384

Contents xlv

26. Papillary Thyroid Carcinoma: Detection of Copy Gain of Platelet Derived Growth Factor B Using Array Comparative Genomic Hybridization in Combination with Laser Capture Microdissection ............................................................................................. 387Stephen P. Finn, John J. O’Leary, and Orla M. SheilsIntroduction ................................................................................................... 387Comparative Genomic Hybridization ........................................................... 387

Vysis GenoSensor Array CGH ................................................................. 389Methodology ................................................................................................. 390

Tumors and Cell Lines .............................................................................. 390Laser Capture Microdissection ..................................................................... 390DNA Extraction ............................................................................................ 391Array Comparative Genomic Hybridization ................................................. 391

Labelling Protocol ..................................................................................... 392DNASE Digestion and Labelled Probe Purifi cation ..................................... 392

Checking the Labelled DNA ..................................................................... 393Hybridization Protocol .................................................................................. 393

Preparing the Reagents ............................................................................. 393Preparing the Hybridization Solution ....................................................... 393Hybridization ............................................................................................ 393Washing the Microarrays .......................................................................... 394

Image Analysis .............................................................................................. 395Results ........................................................................................................... 396

Analysis Cohort ........................................................................................ 396Array CGH ................................................................................................ 396Recurrent Gains and Losses ...................................................................... 396

Discussion ..................................................................................................... 396References ......................................................................................................... 397

27. PET Imaging in Thyroid Carcinoma .......................................................... 399H.H.G. Verbeek, T.T.H. Phan, A.H. Brouwers, K.P. Koopmans, and T.P. LinksIntroduction ................................................................................................... 399Positron Emission Tomography .................................................................... 400

Combined PET/CT.................................................................................... 40118Fluorine-Fluorodeoxyglucose (18F-FDG) ................................................... 401

Mechanism ................................................................................................ 401Scan Method ............................................................................................. 402Clinical Application .................................................................................. 402

18Fluorine-Dihydroxypheny lalanine (18F-DOPA) ......................................... 404Mechanism ................................................................................................ 404Scan Method ............................................................................................. 405Clinical Application .................................................................................. 405

xlvi Contents

11C-Methionine (MET) PET ......................................................................... 406Mechanism ................................................................................................ 406Scan Method ............................................................................................. 407Clinical Application .................................................................................. 407

124I-PET ......................................................................................................... 407Mechanism ................................................................................................ 407Scan Method ............................................................................................. 407Clinical Application .................................................................................. 408

Conclusion .................................................................................................... 409References ......................................................................................................... 411

Therapy

28. Metastasized Medullary Thyroid Carcinoma: Detection and Therapy Using Radiolabeled Gastrin Analogs ................................... 417Martin Gotthardt, Lioe-Fee de Geus-Oei, Thomas M. Behr, and Martin Béhé Medullary Thyroid Carcinoma ..................................................................... 417

Symptoms ................................................................................................. 417Diagnostic Procedures .............................................................................. 417

Localizing and Treating Metastatic Medullary Thyroid Carcinoma ............ 420Radiopeptide Scanning Versus Anatomical Imaging Modalities .................. 421Radiolabeled Peptides ................................................................................... 422Minigastrin for Detecting Metastasized Medullary Thyroid Carcinoma ...... 423

Cholecystokinine 2 (CCK2) Receptor Expression .................................... 424Labeling .................................................................................................... 424Scanning Protocol ..................................................................................... 424Biodistribution of Minigastrin .................................................................. 424Clinical Studies ......................................................................................... 425

Peptide Receptor Radiotherapy of Metastasized Medullary Thyroid Carcinoma with Gastrin Analogs ................................................ 427

Future Perspectives of DGlu1-Minigastrin .................................................... 430References ......................................................................................................... 430

Prognosis

29. Medullary Thyroid Carcinoma: Prognosis based on Stage of Disease and Age ......................................................................... 435Tracy S. Wang, Julie Ann Sosa, and Sanziana A. RomanIntroduction ................................................................................................... 435Epidemiolmogy ............................................................................................. 435Pathology and Pathogenesis of Medullary Thyroid Cancer .......................... 435Clinical Presentation ..................................................................................... 437

Contents xlvii

Diagnostic Testing .................................................................................... 437Genetic Screening ..................................................................................... 437Genotype – Phenotype Correlations ......................................................... 438

Prognostic Factors ......................................................................................... 438Treatment ...................................................................................................... 441

Treatment of Patients with Clinically Evident MTC ................................ 441Prophylactic Surgery for Patients with ret Proto-Oncogene Mutations .... 441Non-Surgical Treatment Modalities .......................................................... 442

Surveillance ................................................................................................... 442References ......................................................................................................... 443

30. Overexpression of the Components of the Plasminogen Activating System as Prognostic Factors in Human Thyroid Carcinoma ....................................................................................... 445Enke Baldini, Salvatore Ulisse, and Massimino D’ArmientoPlasminogen Activating System (PAS) ......................................................... 445The Plasminogen Activating System in Pathophysiological Conditions ...... 446Role of Plasminogen Activating System in Human Cancers ........................ 447Clinical Signifi cance of the Expression of Plasminogen

Activating System Components ................................................................ 448The Plasminogen Activating System in Human Thyroid Carcinomas ......... 449Methods to Evaluate Expression of Plasminogen Activating

System Components.................................................................................. 451Substrate Gel Electrophoresis (Zymograms) ............................................ 451Invasion Assay .......................................................................................... 453Real Time RT-PCR.................................................................................... 454Immunohistochemistry ............................................................................. 455Enzyme-Linked Immunosorbent Assay (ELISA) ..................................... 456

References ......................................................................................................... 457

Index ........................................................................................................................ 459