Contents:

1. Overview 8 1.1 Statement of Report 8 1.2 About This Report 8 1.3 Scope of the Report 9 1.4 Objectives 10 1.5 Methodology 10 1.6 Executive Summary 11 2. Introduction to Cancer Biology and the Diagnostic Industry 14 2.1 Cancer 14 2.1.1 The Disease 14 2.1.2 Metastasis 14 2.1.3 Demographics and Statistics of Cancer 14 2.2 The Drivers of the Biotech and Diagnostics Industry 19 2.2.1 Technological Innovation 20 2.2.2 Government Funding 21 2.3 Outlook for Tumor Markers 21 3. Tumor Markers Market Segment Analysis: Size, Growth and Share 23 3.1 Market Description 24 3.2 Clinical Diagnostic Serum Based Cancer Markers 31 3.3 PSA Testing Market Size 32 3.4 DNA Markers 33 3.5 Serum Proteins 33 3.6 Enzymes 34 3.7 Occult Blood 34 3.8 Histology and In Situ Hybridization (ISH) 35 3.9 Cervical Cytology 36 3.10 Immunohistochemistry 38 3.11 In Vivo Detection Cancer Products 39 3.12 Radionuclides and X-Ray Detection Products 39 3.13 Human Papillomavirus (HPV) Testing 39 3.14 Bladder Cancer Testing 42 3.15 Tumor Assays for Adjuvant Chemotherapy 46 4. Diagnostic Methods for Cancer Detection 60 4.1 Organ Specific Tumor Markers 60 4.1.1 Colon Cancer 60 4.1.2 Prostate Cancer 67 4.1.3 Pancreatic Cancer 84 4.1.4 Breast Cancer 87 4.1.5 Ovarian Cancer 96 4.1.6 Cervical Cancer 101 4.1.7 Lung Cancer 104 4.1.8 Testicular Cancer 107 4.1.9 Bladder Cancer 108 4.1.10 Hepatic Cancer 114 4.1.11 Stomach Cancer 115 4.1.12 Malignant Melanoma 116 4.1.13 Acute Myeloid Leukemia (AML) and Acute Lymphoblastoid Leukemia (ALL) 117 4.1.14 Lymphoma 118 4.2 Clinical Laboratory Methods for Measuring Tumor Markers 118 4.2.1 Abbott Diagnostics AxSYM 118 4.2.2 Roche Diagnostics Elecsys 119 4.2.3 Beckman Coulter Diagnostics Access 119 4.2.4 Bayer Diagnostics ADVIA Centaur 120 4.2.5 Dade Diagnostics Stratus 120 4.2.6 Diagnostic Products Corporation Immulite 120 4.2.7 Tosoh Medics A1A 120 4.2.8 CIS bio International Kryptor 121 4.2.9 Ortho-Clinical Diagnostics Vitros ECiQ 122 4.2.10 Fujirebio Diagnostics, Inc. 122 4.2.11 bioMérieux Vidas 123 4.2.12 Eisai Picolumi 123 4.2.13 Tosoh Medics, Inc. 123 4.3 New Technologies for Cancer Diagnostics 123 4.3.1 New and Improved Immunoassays 124 4.3.2 Immunohistochemical Tests 125 4.3.3 Molecular (DNA and Genomic) Diagnostic Assays 126 4.3.4 Genomics and Genetic Markers 126 4.3.5 Proteomics and New Protein Markers 127 4.3.5.1 Inside the ProteinChip System 128 4.3.5.2 Rapid Biological Assays on a Chip 128 4.3.5.3 Proteome Pattern Recognition 128 4.3.6 New Platform Technologies Including Flow Cytometry 129 4.3.7 Stem Cell Markers 132 4.3.8 Monoclonal Antibodies 132 4.3.9 Proteomics and Cancer Antibodies 135 4.3.10 Pharmacogenomics and Oncology Diagnostics 136 4.3.11 DNA Microarrays 139 4.3.12 In Vitro Diagnostic Multivariate Index Assays (IVDMIA) 141 4.3.13 Prostate PX Score 141 4.3.14 Prostate-63 141 4.3.15 Future Directions 141 4.4 Clinical Methods for Diagnosis of Cancer 142 4.4.1 Screening 142 4.4.2 Sigmoidoscopy 144 4.4.3 Imaging 144 4.4.4 Theranostics 146 5. Implications of Molecular Biology for New Diagnostic Cancer Tests 147 6. Companies Entering the Cancer Diagnostics Market with Novel Technology Platforms 148 6.1 Abbott Diagnostics 148 6.2 Affymetrix, Inc. 149 6.3 Agendia BV 150 6.4 Agensys, Inc. 150 6.5 AMDL, Inc. 151 6.6 Arcturus Bioscience, Inc. 152 6.7 Asuragen, Inc. 153 6.8 Aureon Biosciences Corporation 153 6.9 Bard Diagnostics, Inc. 153 6.10 Bayer Diagnostics 154 6.11 Beckman Coulter, Inc. 154 6.12 Biocode S.A. 156 6.13 BioCurex 156 6.14 Biomedical Diagnostics 156 6.15 Biomerica 157 6.16 bioMérieux 157 6.17 Biomira 157 6.18 BioModa, Inc. 158 6.19 Bruker Daltonics 158 6.20 Byk Gulden 158 6.21 Cepheid 158 6.22 Ciphergen Biosystems, Inc. 159 6.23 Clarient, Inc. 160 6.24 Correlogic Systems, Inc. 162 6.25 Cytogen Corporation 162 6.26 Cytyc Corporation 165 6.27 DiaDexus, LLC 165 6.28 DiagnoCure, Inc. 166 6.29 Diagnostic Products Corporation 168 6.30 Diagnostic Systems Laboratories, Inc. 168 6.31 DRG International, Inc. 168 6.32 Eisai Co., Ltd. 169 6.33 Enigma Diagnostics Ltd. 169 6.34 Epigenomics 169 6.35 Exact Sciences Corporation 170 6.36 Exagen Diagnostics, Inc. 170 6.37 Fujirebio Diagnostics, Inc. 171 6.38 Gene Logic, Inc. 171 6.39 Gen-Probe, Inc. 172 6.40 Genomic Health 172 6.41 Geron Corporation 172 6.42 Immunicon Corporation 173 6.43 Immunomedics, Inc. 177 6.44 Incyte Pharmaceuticals, Inc. 178 6.45 Ipsogen 178 6.46 LabCorp 178 6.47 Matritech 179 6.48 Mitsubishi Kagaku Medical 183 6.49 Molecular Diagnostics, Inc. 183 6.50 Myriad Genetics, Inc. 184 6.51 Poniard Corporation 188 6.52 Nexell Therapeutics, Inc. 189 6.53 Northwest Biotherapeutics, Inc. 190 6.54 Nuvelo 190 6.55 Panacea Pharmaceuticals, Inc. 191 6.56 Oncotech, Inc. 191 6.57 Polymedco, Inc. 192 6.58 Princeton BioMeditech Corporation 193 6.59 Ambrilla Biopharma, Inc. 194 6.60 Qiagen 195 6.61 Sanko Junyaku Co., Ltd. 196 6.62 Tosoh Medics, Inc. 196 6.63 TriPath Imaging, Inc. 196 6.64 UroCor, Inc. 198 6.65 Ventana Medical Systems, Inc. 202 6.66 Veridex 203 6.67 Worldwide Medical Corporation 204 6.68 Xenomics, Inc. 204 7. Business Trends in the Industry 205 7.1 Industry Consolidation 205 7.2 Breath of Product Offering and Pricing 205 7.3 Government Regulation of Medical Devices 206 7.4 Strategic Business and Marketing Considerations 207 7.5 Commercial Opportunities in Cancer Markers 208 7.6 Moderators of Growth 209 7.7 Biotechnology Industry Trends 209 7.8 Pharmaceutical Industry Trends 210 7.9 Acquisition, License Agreement, Partnerships 212 7.10 Legal Developments 214 7.11 Sales and Marketing Strategies for Tumor Marker Tests 215 7.11.1 North American Market 216 7.11.2 International Markets 217 7.11.2.1 Europe 217 7.11.2.2 Central and South America 218 7.11.2.3 Asia/Pacific 218 8. Tumor Marker Testing: Important Issues 219 8.1 Trends in Patient Care and Reimbursement 219 8.2 Trends in Reimbursement Practice 220 8.3 Clinical Laboratory Improvement Act (CLIA) 222 8.4 Unmet Needs in Tumor Markers 223 9. Important New Technology Areas 224 9.1 Proteomics 224 9.2 DNA Sequencing 225 9.3 The Human Genome Project 226 9.4 Liquid Phase Chromatography 227 9.5 Polymerase Chain Reaction (PCR) 227 9.6 Capillary Electrophoresis 228 9.7 Proteomics 229 9.8 Use of Mass Spectroscopy in Sequencing 230 9.9 High-Throughput Organic Synthesis 234 10. New Cancer Markers in Basic Research 236 10.1 Genetics of Cancer 236 10.2 Telomerase 239 10.3 Stomach Cancer 241 10.4 Head and Neck Cancer 242 10.5 Breast Cancer 243 10.6 Prostate Cancer: p27 (Kip1) A New Molecular Marker for Prostate Cancer 244 10.7 PSMA 245 10.8 Cervical Cancer: NMPI79 246 10.9 Pancreatic Cancer: Peritoneal Cytology 246 10.10 Colorectal Cancer: CEA Doubling Time 246 10.11 Uterine and Kidney Cancer: MN/CA9 246 10.12 MMSC1 Scaffold Gene 246 10.13 p16 Tumor Suppressor Gene 247 10.14 MTS2 and p19 Cell Cycle Genes 247 10.15 Complement Factor H Related Proteins 247 10.16 MUC 2, 3, 4 247 10.17 Cytokeratins 248 10.18 Colon Cancer: Serum VEGF 248 10.19 Ras Oncogenes 248 10.20 Lung Cancer: Ribonucleoprotein A2/B1 249 10.21 BCLA-4 Matrix Protein 249 10.22 RAK Antigens 249 10.23 Serum Urokinase Receptors 249 10.24 Chips 250 10.25 Survivin 250 10.26 Human Endometrial Specific Steroid Binding Factor (hESF1) 250 10.27 Reg-4 Protein 251 10.28 Nox-1 251 10.29 PSP94 Binding Protein 251 10.30 Ettan DIGE Technology 251 10.31 YKL-40 252 10.32 AFP-L3 252 10.33 DNA Methylation Technology 252 10.34 Transthyretin and Apolipoprotein A1 252 10.35 ADAM 12 253 10.36 Ovarian Cancer: Ciphergen’s SELDI-based ProteinChip 253 10.37 Lung Cancer: Labeled Porphyrin Binding 253 10.38 C-MAP, A Cervical Cancer Screening System 253 10.39 Lung Cancer: Pro-Gastrin-Releasing Peptide (ProGRP) 253 10.40 Prostate Cancer: PCA3 253 10.41 Bladder Cancer: ImmunoCyt™/uCyt+™ 256 10.42 Shc Proteins 256 10.43 Oncology Biomarker Qualification Initiative 256 10.44 Anti-Glycan Antibodies 257 11. Market Trends and Forecasts 258 11.1 Ultrasensitive Cancer Tests 258 11.2 Mergers and Acquisitions of Diagnostic Companies 259 11.3 RT-PCR 259 11.4 Genetic Tests of Hereditary Cancer Risk 260 11.5 DNA Measurements 260 11.6 Technical and Practical Issues for Potential New Markers 260 11.7 Genetic Profiling 261 11.8 Ploidy 262 11.9 Advances in Sputum Analysis for Screening and Early Detection of Lung Cancer 262 11.10 Pharmacogenetic Tests for Cancer 263 11.11 Worldwide Healthcare Spending 264 11.12 R&D Expenditures 264 Appendix 1: Web Links 265 Appendix 2: Cancer Information Resources 267 Appendix 3: Colon Cancer Staging 268 Appendix 4: Reimbursement for Tumor Marker Testing 269 Appendix 5: The Pathology of Prostate Cancer 271 Appendix 6: Government Regulation of Tumor Marker Tests 273 Appendix 7: The Clinical Laboratory Improvement Act (CLIA) 275 Appendix 8: Marketers of Occult Blood Diagnostic Test Kits 277 INDEX OF FIGURES Figure 4.1: Model of Colorectal Cancer Development Figure 4.2: ASCO-CAP Guidelines for HER2 Testing in Breast Cancer: Equivocal Results with IHC Figure 4.3: ASCO-CAP Guidelines for HER2 Testing in Breast Cancer: Results by FISH Figure 4.4: The BTA stat Test vs. Cytology Figure 6.1: Qiagen Global Sales Figure 10.1: Estimates for PCA3 Test Volume in U.S., 2005-2008 INDEX OF TABLES Table 2.1: Organ-Specific Medicines in Development for Cancer, 2007 Table 2.2: Estimates for the Leading Sites of New Cancer Cases and Deaths in the U.S. by Sex Table 2.3: Estimated Worldwide Number of New Cancer Cases and Deaths by Type of Cancer Table 2.4: Estimated Number of New Cancer Cases and Deaths by Region Table 2.5: Cancer Death Rates per 100,000 Population (and Rank) for all Cancer Sites by Country Table 2.6: Cancer Associated Genes Table 2.7: Carcinogens in the Workplace Table 2.8: Private Funding Levels for the Biotechnology Segment, 1995-2006 Table 2.9: Herceptin Worldwide Sales, 2000-2006 Table 2.10: Classes of Drugs Used to Treat Breast Cancer Table 3.1: In Vitro Cancer Marker Market Segments Worldwide, 2001 and 2007 Table 3.2: Tumor Markers Currently in Common Use Table 3.3: Global IVD Cancer Tumor Marker Testing Market Segments Projected Growth Rates, 2005-2010 Table 3.4: Worldwide Market Size in Dollar Volume for Tumor Marker Assays Product Market, 2001-2010 Table 3.5: U.S. Market Size in Dollar Volume for Tumor Marker Assays Product Market, 2001-2010 Table 3.6: Worldwide In Vitro Cancer Tumor Marker Diagnostics Market Size, 2001-2010 Table 3.7: U.S. In Vitro Cancer Tumor Marker Diagnostics Market Size, 2001-2010 Table 3.8: Japanese In Vitro Cancer Tumor Marker Diagnostics Market Size, 2001-2010 Table 3.9: European In Vitro Cancer Tumor Marker Diagnostics Market Size, 2001-2010 Table 3.10: Global Distribution of IVD Cancer Tumor Marker Diagnostic Testing, 2005 Table 3.11: Estimated Market Share of Major Competitors in U.S. Cancer Tumor Marker Diagnostics Market Table 3.12: Major Presence in Cancer Tumor Marker Diagnostics Markets Table 3.13: Worldwide PSA Sales, 2000-2010 Table 3.14: U.S. PSA Sales, 2000-2010 Table 3.15: Serum Markers Used Clinically Table 3.16: Drivers of IHC Growth Table 3.17: Bladder Cancer Testing Efforts in the U.S. and Germany Table 3.18: Worldwide Bladder Cancer Marker Sales, 2001-2010 Table 3.19: U.S. Bladder Cancer Marker Sales, 2001-2010 Table 3.20: Worldwide NMP22 Sales, 2001-2010 Table 3.21: Current Breast Cancer Product and Product Opportunities Table 3.22: Products in Various Stages of Development for Cancers Other than Breast Cancer Table 4.1: Colorectal Cancer Stages Table 4.2: Worldwide CEA Sales, 2001-2010 Table 4.3: U.S. CEA Sales, 2001-2010 Table 4.4: Population Statistics of Serum Levels of PSA in Men Over 50 Years of Age Table 4.5: PSA Doubling Time and Time to Reach PSA of 1,000 Table 4.6: PSA Doubling Times Table 4.7: Worldwide CA19-9 Sales, 2001-2010 Table 4.8: U.S. CA19-9 Sales, 2001-2010 Table 4.9: CA19-9 Levels in Management of Pancreatic Cancer Table 4.10: Worldwide CA15-3 Sales, 2001-2010 Table 4.11: U.S. CA15-3 Sales, 2001-2010 Table 4.12: TPA Marker Sensitivity Table 4.13: ASCO-CAP Guidelines for HER2 Testing in Breast Cancer: How to Interpret Test Results Table 4.14: Siemens Oncogene Science Biomarker Group Reagents Table 4.15: Worldwide CA-125 Sales, 2001-2010 Table 4.16: U.S. CA-125 Sales, 2001-2010 Table 4.17: Number of Pap Smears Performed by Country Table 4.18: Lung Cancer Facts Table 4.19: Patient Category Applications Table 4.20: Worldwide AFP Marker Sales, 2001-2010 Table 4.21: U.S. AFP Cancer Marker Sales, 2001-2010 Table 4.22: Potential Uses of Molecular Diagnostics in Cancer Management Table 4.23: Colorectal Cancer Monoclonal Antibody Imaging Kits Table 6.1: Product Sales as a Percent of Total Product Sales, 2004-2006 Table 6.2: Tumor Diagnosis Immunoassay Table 6.3: Tumor Diagnosis Radioimmunoassay Table 6.4: Summary of Matritech’s Product Development Programs Table 6.5: Statements of Operations Data for Matritech, 2002-2006 Table 6.6: Results of Operations of Matritech, 2005 and 2006 Table 6.7: PBM Product List Table 7.1: List and Discounted Prices for Abbott Tumor Marker Tests Table 8.1: CPT Codes for Tumor Markers Table 10.1: Familial Cancer Syndromes and Tumor Suppressor Genes Table 10.2: Oncogenes and Anti-oncogenes Table A3: TNM Classification Table A7: Financial Comparison for Moderate and Waived CLIA Labs Table A8: List of Marketers of Occult Blood Diagnostic Test Kits