| Publications by Biophoenix' Principals |
| In vitro Cancer Diagnostics II | |
|---|---|
 | |
| Publisher: | PJB Publications Ltd |
| Year of publication: | 1993 |
| Type of publication: | Management report |
| Publisher's reference (if any): | CBS 330 |
| Author(s): | Sreten Bogdanovic |
| Approximate page count: | 250 |
| Price when published: | £350 |
Remarks:
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IN VITRO CANCER DIAGNOSTICS
Second Edition
A market overview prepared for
Clinica World Medical Device and Diagnostic News
(c) January 1993 by PJB Publications
CONTENTS
Page
CONTENTS i
EXECUTIVE SUMMARY viii
CHAPTER 1 THE NATURE AND MANAGEMENT OF CANCER
1.1 Cancer as a public health problem 1
1.2 Scope of this report 1
1.3 The nature of cancer 3
1.3.1 Environmental and lifestyle factors 3
1.3.2 Control of growth rate 3
1.3.3 Role of the immune system 3
1.3.4 Tumour initiation 4
1.3.5 Tumour promotion 4
1.3.6 Tumour progression 5
1.3.7 Characteristics of malignant cells 5
1.3.8 Types of tumour 5
1.3.9 Metastasis 5
1.3.10 Death from cancer 7
1.4 Nomenclature of cancer 7
1.4.1 Types of growth 7
1.4.2 Types of body tissue 7
1.4.3 Types of cell 7
1.4.4 Types of tumour 8
1.5 Role of diagnostic tests in cancer management 9
1.5.1 Importance of diagnostic accuracy 9
1.5.2 Types of `diagnosis' 9
1.5.3 Screening 10
1.5.3.1 Efficacy of screening 10
1.5.3.2 Requirements for screening 10
1.5.3.3 Quantitative aspects of screening 10
1.5.3.4 Case study: screening for
prostate cancer 12
1.5.3.4.1 Clinical background 12
1.5.3.4.2 PAP as a screening test
for prostate cancer 13
1.5.3.5 Screening using multiple markers
and decision support systems 14
1.5.4 Diagnosis, prognosis, and monitoring 16
1.5.4.1 Definitions 16
1.5.4.2 Tumour staging 17
1.5.4.3 Tumour grading 17
1.5.4.4 Tumour monitoring 18
1.6 Survey of in vivo cancer diagnostics 19
1.6.1 Introduction 19
1.6.2 Physical examination and endoscopy 20
1.6.3 Diagnostic radiology 20
1.6.4 Nuclear imaging 21
1.6.5 Magnetic resonance imaging 22
1.6.6 Ultrasonography 23
1.7 Overview of in vitro cancer testing 23
1.7.1 Introduction 23
1.7.2 Histology and cytology 24
1.7.3 Clinical chemistry 26
1.7.4 Immunodiagnostic tests in cancer 26
1.7.5 DNA diagnostics 27
1.7.6 Use of instrumentation 28
1.8 Treatment of cancer 29
1.8.1 Introduction 29
1.8.2 Surgery 29
1.8.3 Radiotherapy 30
1.8.4 Chemotherapy 31
1.9 Exchange rates used in this report 33
CHAPTER 2 SURVEY OF COMMON CANCERS
2.1 Introduction 35
2.1.1 The ten commonest cancers 35
2.1.2 Overview of epidemiology 35
2.1.3 Aetiological factors in cancer 37
2.2 Lung cancer 38
2.3 Cancer of the stomach 40
2.4 Cancer of the breast 43
2.5 Colorectal cancer 45
2.6 Cervical cancer 47
2.7 Haematogenous malignancies 48
2.8 Oropharyngeal tumours 51
2.9 Oesophageal cancer 51
2.10 Primary liver cancer 52
2.11 Cancer of the prostate 53
2.12 Conclusions for in vitro diagnostics 54
CHAPTER 3 IMMUNOASSAYS IN CANCER DIAGNOSTICS
3.1 Introduction 56
3.2 Principles of immunoassays 56
3.2.1 General characteristics of immunoassays 56
3.2.2 Labelling 57
3.2.3 Bound-free separation 58
3.2.4 Competitive immunoassays 59
3.2.5 Immunometric immunoassays 60
3.2.6 Monoclonal antibodies 61
3.2.6.1 Comparison with conventional antisera 61
3.2.6.2 Antigenic determinants 62
3.2.6.3 Monoclonal antibody preparation 62
3.2.6.4 Advantages of monoclonal antibodies 62
3.2.6.5 Future developments 63
3.2.6.6 Monoclonal antibodies and DNA probes 63
3.2.7 Homogeneous immunoassays 64
3.2.8 Standardisation of immunoassays 65
3.2.9 Matrix effects 67
3.2.10 Sensitivities and detection limits 68
3.3 Commercial immunoassay formats 69
3.3.1 Kits and systems 69
3.3.2 Commercial radioimmunoassays 70
3.3.3 Commercial enzyme immunoassays 70
3.3.4 Commercial fluoroimmunoassays 71
3.3.5 Commercial luminescent immunoassays 71
3.3.6 Automation of commercial immunoassay systems 72
3.4 Survey of individual analytes 73
3.4.1 Carcinoembryonic antigen (CEA) 75
3.4.2 Alpha-foetoprotein (AFP) 76
3.4.3 Human chorionic gonadotrophin (hCG) 77
3.4.4 Prostatic acid phosphatase (PAP) 79
3.4.5 Prostate-specific Antigen (PSA) 81
3.4.6 CA 125 81
3.4.7 CA 215 82
3.4.8 CA 19-9 83
3.4.9 CA 19-5 83
3.4.10 CA 50 83
3.4.11 CA 72-4/TAG-72 84
3.4.12 CA 15-3 84
3.4.13 CA 549 84
3.4.14 CA 494 85
3.4.15 BCA 225 85
3.4.16 Polymorphic epithelial mucin 85
3.4.17 CA M26 and CA M29 86
3.4.18 Mammary carcinoma antigen 86
3.4.19 pS2 86
3.4.20 Cathepsin D 87
3.4.21 Urokinase-plasminogen activator 87
3.4.22 Neuron-specific enolase (NSE) 88
3.4.23 Neural cell adhesion molecule 88
3.4.24 Cytokeratins 88
3.4.25 S-100 89
3.4.26 p53 89
3.4.27 gp170 91
3.4.28 Squamous cell carcinoma antigen/Ta-4 91
3.4.29 Tissue polypeptide antigen (TPA) 92
3.4.30 Beta-2-microglobulin 93
3.4.31 Ferritin 93
3.4.32 Thyroglobulin 93
3.4.33 Creatine kinase (brain isoenzyme) 94
3.4.34 Placenta-like alkaline phosphatase 94
3.4.35 Fibrin degredation products 94
3.4.36 Oncogene products: erb-B2/neu 95
3.4.37 Helicobacter pylori antibodies 96
3.4.38 Antineoplastic drug monitoring 96
3.4.39 Hormone receptors 97
3.4.39.1 Introduction 97
3.4.39.2 Radioreceptor assays 97
3.4.39.3 Immunoassays and immunohistochemistry 98
3.4.39.4 Receptor assays in breast cancer 98
3.4.39.5 Receptor assays in prostate cancer 99
3.4.39.6 Receptor assays in other tumours 99
3.4.40 Immunoassays in endocrine tumours 100
3.4.40.1 Special features of endocrine tumours 100
3.4.40.2 Grading endocrine tumours 100
3.4.40.3 Staging endocrine tumours 101
3.4.40.4 Survey of endocrine tumours by organ 101
3.4.40.4.1 Adrenal cortex 102
3.4.40.4.2 Pituitary gland 102
3.4.40.4.3 Pancreas 102
3.4.40.4.4 Prevalence of endocrine
activity in tumours 103
3.4.40.5 Survey of specific endocrine tumours 103
3.4.40.5.1 Ovarian and adrenocortical
malignancies 103
3.4.40.5.2 Testicular tumours 104
3.4.40.5.3 The carcinoid syndrome
and carcinoid tumours 104
3.4.40.5.4 Thyroid cancer 105
3.4.40.5.5 Multiple endocrine neoplasia 106
3.4.40.5.6 Insulinomas 107
3.4.40.5.6.1 Clinical features
and diagnosis 107
3.4.40.5.6.2 Immunoguided surgery 108
3.4.40.5.7 VIPomas 109
3.4.40.5.8 PP-omas 109
3.4.40.5.9 Vasopressinomas 109
CHAPTER 4 HISTOLOGY/CYTOLOGY DIAGNOSTICS
4.1 Introduction 111
4.2 Automation in histology and cytology 111
4.2.1 Automation in histology 111
4.2.2 Automation in cytology 112
4.2.3 Conclusions 113
4.3 Histology 113
4.3.1 Overview of applications 113
4.3.2 Routine histopathology 113
4.3.3 Immunohistopathology 114
4.3.3.1 Antibodies 114
4.3.3.2 Tissue type (MHC) antigens 114
4.3.3.3 Adhesion molecules 115
4.3.3.4 Tumour-associated proteins
and endocrine peptides 115
4.3.3.5 Intermediate filaments 115
4.3.3.6 Receptors 116
4.3.3.7 Leucocyte cell surface markers 116
4.3.3.8 Tumour chemosensitivity testing 116
4.3.3.9 Availability of immunohisto-
pathology reagents 116
4.4 Cytology 120
4.4.1 Introduction 120
4.4.2 Flow cytometry 120
4.4.2.1 Overview of applications 120
4.4.2.2 Performance 121
4.4.2.3 Fluorophores 122
4.4.2.4 Presentation of results 122
4.4.2.5 Flow cytometric markers 123
4.4.2.6 Flow karyotyping 123
4.4.2.7 Flow sorting 128
4.4.2.8 Availability of instruments
and reagents 129
4.4.3 Manual immunophenotyping 130
4.4.4 Diagnosis of immunodeficiency in oncology 130
4.4.4.1 Diagnostic overview 130
4.4.4.2 Cancer-related immunodeficiencies 130
4.4.4.3 Neutropenia 132
4.4.4.4 Antibody deficiencies 132
4.4.4.5 Cellular immunodeficiencies 132
4.4.5 Cervical cytology 133
4.4.5.1 Clinical overview 133
4.4.5.2 Conventional procedures 134
4.4.5.3 Grading using the CIN system 134
4.4.5.4 Availability of reagents 135
4.4.5.5 Role of human papillomavirus (HPV) 135
4.4.5.6 DNA typing of HPV 135
CHAPTER 5 CLINICAL CHEMISTRY DIAGNOSTICS
5.1 Introduction 137
5.2 Enzyme assays and immunoassays 137
5.3 Use of clinical chemistry tests in cancer 138
5.4 Faecal occult blood tests 139
5.4.1 Clinical overview 139
5.4.2 Take-up of colorectal screening 139
5.4.3 Methodology of the basic guaiac test 140
5.4.4 Shortcomings of the guaiac test 140
5.4.5 Modified faecal tests 141
5.4.5.1 Fluorimetric techniques 141
5.4.5.2 Immunoassay techniques 142
5.4.5.3 DNA diagnostic techniques? 142
5.5 Urinary occult blood 142
5.6 Alkaline phosphatase 143
5.7 Acid phosphatase 143
5.8 Gamma-glutamyltransferase 144
5.9 Lactate dehydrogenase 144
5.10 5'-nucleotidase 144
5.11 Amylase 144
5.12 Thymidine kinase 145
5.13 Alpha-fucosidase and galactosyltransferase 145
5.14 Ornithine decarboxylase 145
5.15 Elastase 146
5.16 DOPA decarboxylase 146
5.17 Catecholamines 147
5.18 17-ketosteroids 147
5.19 Sialic acids 147
5.20 Lysozyme (muramidase) 148
5.21 Creatine kinase (brain isoenzyme) 148
5.23 Serum protein assays 148
5.24 Other clinical chemistry analytes 149
CHAPTER 6 DNA DIAGNOSTICS
6.1 Introduction 152
6.2 Molecular biology of cancer 152
6.2.1 Introduction to DNA 152
6.2.2 DNA and genes 152
6.2.3 The structure of DNA 152
6.2.4 DNA and chromosomes 154
6.2.5 Chromosomes and genes 154
6.2.5.1 Alleles 154
6.2.5.2 Heterozygosity and polymorphism 154
6.2.5.3 Genetic linkage 155
6.2.5.4 Recombination 155
6.2.5.5 Genetic mapping 156
6.2.6 Chromosomes and cytogenetics 157
6.2.6.1 Nomenclature 157
6.2.6.2 Chromosomal aberrations 157
6.2.6.3 Karotypes 158
6.2.6.4 DNA methods in cytogenetics 158
6.3 Molecular events in tumour formation 160
6.3.1 Somatic and germ-line mutations 160
6.3.2 Viruses and cancer 160
6.3.3 Oncogenes 161
6.3.3.1 Nature of oncogenes 161
6.3.3.2 Mode of action of oncogenes 163
6.3.4 Inheritance of cancer 166
6.3.4.1 Introduction 166
6.3.4.2 Retinoblastoma and anti-oncogenes 168
6.3.4.3 Other deletion-associated malignancies 168
6.3.4.4 Conclusions 169
6.4 An introduction to DNA probes 170
6.4.1 Nature of DNA probes 170
6.4.2 Use of DNA probes in cancer diagnostics 171
6.4.3 Oligonucleotide (i.e. short) probes 171
6.4.4 Long (genomic or cDNA) probes and RFLPs 172
6.4.5 Southern blotting 173
6.4.6 DNA amplification 175
6.4.6.1 Introduction to PCR 175
6.4.6.2 Power of PCR 175
6.4.6.3 Principles of PCR 176
6.4.6.4 DNA amplification in the marketplace 178
6.5 Specific applications of DNA diagnosis to cancer 179
6.5.1 Oncogene assays 179
6.5.2 bcr analysis 180
6.5.3 B/T cell DNA analysis 180
6.5.4 Other haematogenous malignancies 181
6.5.5 DNA tests in cervical cancer 182
6.5.5.1 Potential role of DNA tests 182
6.5.5.2 DNA assays in HPV typing 182
6.5.5.3 Some caveats 183
6.5.5.4 Availability of HPV DNA tests 184
6.5.6 Commercial availability of
DNA diagnostic products 184
CHAPTER 7 COMPANIES AND MARKETS
7.1 Introduction 187
7.2 Market analysis 187
7.2.1 Demographic factors 187
7.2.2 Geographical factors 189
7.2.2.1 Overview of cancer management worldwide 189
7.2.2.2 USA 191
7.2.2.3 Western Europe 192
7.2.2.4 Japan 193
7.2.3 Cancer screening worldwide 193
7.2.4 Product-specific marketing factors 195
7.2.5 Sales analysis and forecasts to 1997 195
7.2.5.1 Introduction 195
7.2.5.2 Immunoassays 196
7.2.5.3 Clinical chemistry 200
7.2.5.4 Histology and cytology 205
7.2.5.5 DNA diagnostics 206
7.2.5.6 Instruments 207
7.3 Market leaders and competitive structure 207
7.4 Market opportunities 210
7.5 Company profiles 211
7.5.1 Introduction 211
7.5.2 Abbott Laboratories 211
7.5.3 Ares-Serono 213
7.5.4 Baxter Healthcare 213
7.5.5 Becton Dickinson 214
7.5.6 Behring 215
7.5.7 Biomerica 216
7.5.8 Boehringer Mannheim 216
7.5.9 Centocor 218
7.5.10 Cetus 220
7.5.11 CIS Bioindustries 221
7.5.12 Diagnostic Products 222
7.5.13 Hybritech 223
7.5.14 Kabi-Pharmacia 225
7.5.15 Oncogene Science 226
7.5.16 Oncor 226
7.5.17 Roche Diagnostic Systems 227
7.5.18 Sanofi-Diagnostics Pasteur 228
7.5.19 Sorin Biomedica 229
APPENDIX 1 CORPORATE DIRECTORY 231
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