Molecular Mechanisms of Basal Cell and Squamous Cell Carcinomas

148 Pages·2006·4.695 MB·English

by  Jörg Reichrath (auth.)

MEDICAL
INTELUGENCE
UNIT
Molecular Mechanisms
of Basal Cell and
Squamous Cell Carcinomas
Jorg Reichrath, Prof. Dr. med.
The Saarland University Hospital
Clinic for Dermatology, Allergology and Venerology
Homburg/Saar, Germany
LANDES BIOSCIENCE / EUREKAH.COM SPRINGER SCIENCE+BUSINESS MEDIA
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MOLECULAR MECHANISMS OF BASAL CELL
AND SQUAMOUS CELL CARCINOMAS
Medical Intelligence Unit
Landes Bioscience / Eurekah.com
Springer Science+Business Media, Inc.
ISBN: 0-387-26046-3 Printed on acid-free paper.
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9 8 7 6 5 4 3 21
Library of Congress Cataloging-in-Publication Data
Molecular mechanisms of basal cell and squamous cell carcinomas / [edited by] Jorg Reichrath.
p. ; cm. ~ (Medical intelligence unit)
Includes bibliographical references and index.
ISBN 0-387-26046-3 (alk. paper)
1. Skin~Cancer~Genetic aspects. 2. Basal cell carcinoma—Genetic aspects. 3. Squamous cell carcinoma-
Genetic aspects. I. Reichrath, J. (Jorg), 1962- 11. Title. III. Series: Medical intelligence unit (Unnumbered
: 2003)
[DNLM: 1. Carcinoma, Basal Cell—genetics, 2. Carcinoma, Basal Cell—physiopathology. 3. Carcinoma,
Squamous Cell—genetics. 4. Carcinoma, Squamous Cell—physiopathology. 5. Cytogenetics—methods. 6.
Papillomavirus Infections—complications. QZ 365 M718 2006]
RC280.S5M65 2006
616.99'477042-dc22
2006005864
About the Editor
JORG REICHRATH is Professor of Dermatology and Deputy Director
of the Clinic for Dermatology, Allergology and Venerology at the Saarland
University Hospital in Homburg/Saar, Germany. Main research interests include
carcinogenesis and treatment of non-melanoma skin cancer and melanoma.
He is a member of numerous national and international scientific organizations,
including the German Dermatological Society (DDG), the Deutsche
Krebsgesellschaft (DKG), the German Dermatologic Co-operative Oncology
Group (DeCOG), and the European Society of Dermatological Research (ESDR).
Jorg Reichrath received his academic degrees (Dr. med., venia legendi) from the
Saarland University, Germany.
Dedication
I dedicate this book to Univ.-Prof. Dr. med. Wolfgang Tiigen,
my teacher in dermato-oncology.
CONTENTS
Preface XV
1. The Epidemiology of Basal Cell and Squamous Cell Carcinoma 1
Hao Wang and Thomas L. Diepgen
Incidence of NonmelanomaSkin Cancer (NMSC) 1
Trends in Incidence of BCC and SCC 3
Risk Factors 3
Ultraviolet Radiation (UVR) 3
Ageing 4
Smoking 4
Alcohol 4
Diet 4
Medical Conditions 5
Ionizing Radiation 5
Occupation 5
Chemical Carcinogens 6
History and Precursor Lesions 6
Skin Cancer Prevention Strategies 6
2. Histology of Epithelial Skin Tumors 10
Jorg Reichrath andKerstin Querings
Squamous Cell Carcinoma 10
Basal Cell Carcinoma 15
Basosquamous Carcinoma 16
3. UV Damage and DNA Repair in Basal Cell
and Squamous Cell Carcinomas 18
Knuth Rass
UV Damage and DNA Repair 19
UV-Induced Carcinogenesis in Squamous Cell Carcinoma (SCC) 23
UV-Induced Carcinogenesis in Basal Cell Carcinoma (BCC) 25
4. Papillomavirus Infections and Cancerogenesis of Squamous Cell
and Basal Cell Carcinomas 31
Guido Bens
Basal Cell Carcinomas 39
5. The Immune System and Nonmelanoma Skin Cancers 43
Elma D. Baron
Epidemiologic Evidence from Organ Transplant Recipients 43
Evidence from Studies on UV-Induced Immune Suppression
and Nonmelanoma Cancer Formation 44
Mechanisms Involved in Immune Suppression and Carcinogenesis
of Nonmelanoma Skin Tumors 45
6. Cytogenetics of Basal Cell Carcinoma
and Squamous Cell Carcinomas 49
MelanieA. CarlesSy Kevin]. Ashton andLyn R Griffiths
Cytogenetic Analysis 49
Ploidy Analysis 50
Classical Karyotypic Analysis 51
Fluorescence in Situ Hybridization Analysis
and Comparative Genomic Hybridization Analysis 51
Implications of Cytogenetic Findings and Future Developments 53
7. The Hedgehog Signaling Pathway and Epithelial Skin Cancer 58
Julia Reifenherger
The Hedgehog Signaling Pathway 59
Alterations of Hedgehog Signaling in Skin Tumors 60
Mouse Models for Basal Cell Carcinoma 62
Novel Pathogenesis-Based Approaches for Prevention
and Therapy of Basal Cell Carcinomas 63
8. p53 Protein and Nonmelanoma Skin Cancer 66
Vladislava O. Melnikova and Honnavara N. Ananthaswamy
p53 Tumor Suppressor Gene 66
Induction of p53 Protein by UV and Biologic Consequences 69
A Model of UV-Induced Initiation and Progression
of Squamous Cell Carcinomas 69
p53 Mutations in Nonmelanoma Skin Cancers 69
p53 Mutations in Mouse Skin Cancers 72
9. TGF-p Pathway and Cancerogenesis of Epithelial Skin Tumors 80
Miguel Quintanilla, Eduardo Pirez-Gdmez, Diana Romeroy
Mar Pons and]aime Renart
TGF-p Signalling 80
Role of TGF-P in Epidermal Development 82
Role of TGF-P in Epidermal Proliferation and Homeostasis 84
Role of TGF-p in Epithelial Skin Cancer 86
10. PDGF Pathways and Growth of Basal Cell
and Squamous Cell Carcinomas 94
Jingwu Xie
Signal Transduction by PDGFs and Their Receptors 94
In Vivo Functions of PDGFs and Their Receptors 95
PDGF Alterations in Cancer 97
The Role of PDGF for Cell Proliferation in BCCs 99
The Role of PDGFA^GF Signaling in Angiogenesis of SCCs 102
PDGF Signaling in Dermatofibrosarcoma Protuberans
and Giant Cell Fibroblastoma 104
Perspectives 104
11. Apoptosis and Cancerogenesis of Basal Cell
and Squamous Cell Carcinoma 108
Peter Erb, Jingmin Jiy Marion Wemli and Stanislaw A. Buchner
Gene Mutations Lead to NMSCs 109
Apoptosis Is Pivotal for the Removal of DNA Damaged
and Transformed Cells 110
UV-Light Changes the Expression Pattern of Apoptosis-Inducing
and -Preventing Molecules in Skin Epidermis 110
FasL, the Double-Edged Sword Ill
Downregulation of FasL on BCC by Antisense Oligonucleotides
or Small Interfering RNAs (siRNAs) 112
Outlook 113
12. The Role of Telomerase for Cancerogenesis of Basal Cell
and Squamous Cell Carcinomas 115
Eva-Maria Fahricius
Interaction of Telomeres and Telomerase 116
Telomerase Activating in Normal Skin 119
Telomerase Activation in the Nonmelanoma Skin Tumors BCC
and sec and in Their Tumor-Free Margins 121
Index 135
EDITOR
Jorg Reichrath
The Saarland University Hospital
Clinic for Dermatology, Allergology and Venerology
Homburg/Saar, Germany
Email: [email protected]
Chapter 2
CONTRIBUTORS^
Honnavara N. Ananthaswamy Stanislaw A. Biichner
Department of Immunology Department of Dermatology
The University of Texas M.D. Anderson University Hospitals
Cancer Center Basel, Switzerland
Houston, Texas, U.S.A. Chapter 11
Email: [email protected]
Chapter 8 Melanie A. Carless
Genomics Research Centre
Kevin J. Ashton School of Health Science
Genomics Research Centre Griffith University Gold Coast
School of Health Science Bundall, Queensland, Australia
Griffith University Gold Coast Chapter 6
Bundall, Queensland, Australia
Chapter 6 Thomas L. Diepgen
Department of Clinical Social Medicine,
Elma D. Baron Occupational and Environmental
Department of Dermatology Dermatology
Skin Study Center University Hospital Heidelberg
University Hospitals of Cleveland Heidelberg, Germany
Case Western Reserve University Email:
Cleveland, Ohio, U.S.A. [email protected]
Email: [email protected] Chapter 1
Chapter 5
Peter Erb
Guido Bens Institute for Medical Microbiology
The Saarland University Hospital University of Basel
Clinic for Dermatology, Allergology Basel, Switzerland
and Venerology Email: [email protected]
Homburg/Saar, Germany Chapter 11
Email: [email protected]
Chapter 4
Eva-Maria Fabricius Kerstin Querings
Clinic for Oral and Maxillofacial Surgery The Saarland University Hospital
Campus Virchow Hospital Clinic for Dermatology, Allergology
Medical Faculty of the Humboldt and Venerology
University of Berlin Charit^ Homburg/Saar, Germany
Berlin, Germany Chapter 2
Email: [email protected]
Chapter 12 Miguel Quintanilla
Instituto de Investigaciones Biom^dicas
Lyn R. Griffiths Alberto Sols
Genomics Research Centre Consejo Superior de Investigaciones
School of Health Science Cientfficas-Universidad Aut6noma
Griffith University Gold Coast de Madrid
Bundall, Queensland, Australia Madrid, Spain
Email: [email protected] Email: [email protected]
Chapter 6 Chapter 9
Jingmin Ji Knuth Rass
Institute for Medical Microbiology The Saarland University Hospital
University of Basel Clinic for Dermatology, Allergology
Basel, Switzerland and Venerology
Chapter 11 Homburg/Saar, Germany
Email: [email protected]
Vladislava O. Melnikova Chapter 3
Department of Immunology
The University of Texas M.D. Anderson Jtdia Reifenberger
Cancer Center Department of Dermatology
Houston, Texas, U.S.A. Heinrich-Heine-Universitat
Chapter 8 Dusseldorf, Germany
Email:
Eduardo P^rez-G6mez reifenbergerj @med. uni-duesseldorf de
Instituto de Investigaciones Biom^dicas Chapter 7
Alberto Sols
Consejo Superior de Investigaciones Jaime Renart
Cientfficas-Universidad Aut6noma Instituto de Investigaciones Biom^dicas
de Madrid Alberto Sols
Madrid, Spain Consejo Superior de Investigaciones
Chapter 9 Cientfficas-Universidad Aut6noma
de Madrid
Mar Pons Madrid, Spain
Instituto de Investigaciones Biom^dicas Chapter 9
Alberto Sols
Consejo Superior de Investigaciones
Cientfficas-Universidad Autdnoma
de Madrid
Madrid, Spain
Chapter 9