45/B-B3 34–5, 130 17-1-A antibody 57–8
acute lymphocytic leukaemia (ALL) 1 adjuvant breast cancer therapy 47–59 AE1/AE3 128 (table), 131, 133
␣/ catenin 56
American College of Surgeons Oncology Group (ACOSOG) protocol 81
amplification 31 AmpliTaq 36
androgen ablative therapy 88–9 androgen receptor status 87 androgen-regulated genes 102
anti-human epithelial antigen (anti-HEA) 103 anti-lactadherin 7, 8 (fig.)
antiBA46 7, 8 (fig.) antibody P717 7, 8 (fig.) antibody-based immunotherapy 48 antigen-antibody interaction 19 antikeratin antibodies 78 antimucin antibodies 78
array-Comparative Genomic Hybridisation (array- CGH) 87
autologous stem cell transplantation therapy 76 axillary lymph node dissection (ALND) 80–1
BA46 4, 7 BA70 4, 7
Ber-EP4 99, 118–19, 128
esophageal carcinoma 128 (table), 132 non-small cell lung cancer 118–19 Ber-EP4 see also epCAM antigen
 actin 5
blood see peripheral blood bone marrow
assessment
colorectal carcinoma 144–8
esophageal carcinoma, immunocytochemical detection 129–30
gastric carcinoma 151 pancreatic carcinoma 155, 160 breast cancer
assessment 34 detection 47–59, 71–6 prognostic relevance 49–50 progression 74
cancer spread 67
non-small cell lung carcinoma, tumour cell detection 121–3
solid tumours, dissemination 1
TNM staging, correlation 74 vasculature 72
bone metastasis breast cancer 47–8 prostate cancer 87 brachytherapy 88
breast-associated antigens 4 breast cancer
adjuvant therapy 47–59
cell-cycle independent treatment 48 lymph node negative disease 71 AE1 78
antibody-based immunotherapy 48 bone marrow
assessment 34
occult metastatic detection 47–59, 71–6 CAM5.2 78
lymph nodes assessment 51–2 micrometastases
biological characteristics 52–6
detection, peripheral blood vs. bone marrow 71–81
flow cytometry 71 immunohistochemistry 68 molecular methods 68–71 multi-institutional studies 74–5, 81 prognostic relevance 48–52 prognostic importance 81
Ca19-9 155 CAM5.2 antibody
colorectal carcinoma 141, 144 gastric carcinoma 148 cancer
cells, chromosomal changes 31
recurrent disease, after primary therapy 67, 71 carcinoembryonic antigen (CEA) 3, 69
esophageal carcinoma 128 carcinogenic agents 22–3 catenins 56
cDNA array hybridization 102 chemo-resistance 48
chemoradiotherapy, head and neck cancer 20 chemotherapy, cytotoxic regimes 57–8 chromosome 11q13 4
chronic myeloid leukaemia (CML), bcr/abl- rearrangement 2
circulating tumour cells 34 13-cis-retinoic acid 23 CK2 antibody 121
INDEX
colorectal carcinoma 139 bone marrow 144–8
haematogenous dissemination 139 lymph nodes 141–4
peripheral blood 148 peritoneal lavage 148
comparative genomic hybridization (CGH) 101–2, 106
computed tomography, tumour staging 21 contamination, tumour cells 29–30 Crohn’s disease 8
cytogenetic technique, prostate cancer 89 cytokeratin-18 6, 34, 69, 99, 121, 141 cytokeratin-19 6–7, 34–5, 69, 99, 141 cytokeratin-20 4, 6, 10–11, 69, 144, 151 cytokeratin-2 144
cytokeratin-8 34, 99, 141 cytokeratin(s) 2–4, 48
esophageal carcinoma 127 reticular cells 118 cytotoxic antibodies 56–7
deletion 31
denaturing-HPLC 28–9
density gradient centrifugation 94, 98 desmoplakin I 69
digital-PCR 25 disseminated tumour cells
detection, molecular methods 1–15 solid cancer cells, target sequences 3–4 molecular markers 34–9
tumour-biological therapies 47–59 DNA polymerase 30
dormancy, disseminated tumour cells 48, 53–4 duplication 31–2
E-48 antigen 35–7 gene expression 25 E-48 RT-PCR assay 35–7 E-cadherin 54, 56 edrecolomab 57–8 ENTREZ 13
EORTC Melanoma Group 171, 178
EpCAM antigen 53(table), 56, 99, 124, 128(table) epithelial cancer dissemination, detection 2–3 epithelial cell adhesion molecules 53(table), 55–6,
99
epithelial glycoprotein-40 (EGP-40) 69 epithelial growth factor (EGF) 4, 54
receptor 53(table) erb-B2 oncogene 52, 69
over-expression 54–5
erb-B3 prostate specific membrane antigen 69 esophageal carcinoma 127–35, 130
early tumour relapse 127
immunocytochemical tumour cell detection 129–30
immunohistochemical tumour cell detection 130–3 nucleic acid-based approaches 133–4
survival rates 127
exonuclease amplification coupled capture technique point (EXACCT) 101–2
external beam radiation therapy 88
FACS analysis 4
Ficoll centrifugation 11–13 Ficoll-Hypaq 91, 98, 103, 175 Ficoll-Paque 91
field cancerization 22–3, 34 flow cytometry
occult metastases detection breast cancer 68–71 esophageal carcinoma 130 prostate cancer 87, 92–3 fluorescent in situ hybridization (FISH)
prostate cancer 100 cells, detection 87 flutamide 90 follicular lymphoma 2
GA-733-2 gene 56
gastric carcinoma 139, 148–51 bone marrow 151
clinical studies 141 lymph nodes 148 peripheral blood 151 peritoneal lavage 151 gastrointestinal carcinoma
mortality 139 survival rates 139
gastrointestinal tumour-associated antigen 733.2 (GA 733.2) 69
gene chips 102
gene expression, micro-arrays 87, 102 Gleason score 88–9, 92
haematological malignancies 1 head and neck cancer
prognosis 19 TNM staging 21
see also head and neck squamous cell carcinoma
head and neck squamous cell carcinoma 19–39 chemoprevention 23
disseminated tumour cells, molecular markers 34–9
field cancerization 22
fields detection, microsatellites as markers 31–4 lymph nodes, locoregional control 20
metastases, distant 20
resection, surgical techniques 20 second primary tumour 21–3
surgical margins, molecular assessment 23–31 survival rate 20
TNM staging 21 treatment failure 19
hereditary non-polyposis colorectal carcinoma (HNPCC) 33
HLA class I molecules 53 (table), 55 hormonal receptor genes 4
human epithelial antigen (HEA) 98–9 human glandular kallikrein 94, 97 human milk fat complex, proteins 4 HUSAR 13
“illegitimate” gene expression 13–14 immunocytochemical assays 1–2, 4, 34–5
head and neck cancer 34–5 sensitivity 14
immunohistochemistry
breast cancer, occult metastases 68 prostate cancer cells, detection 87, 91–2 immunological anti-tumour defence, relevant
proteins 55
immunomagnetic cancer cell enrichment 14
“informative” marker 32
␥-interferon 9
International Breast Cancer Study 79–80 International Union Against Cancer (UICC)
staging classification 135, 140
TNM classification 119 (table), 120, 122–3
K-ras mutations 24 tumour cell detection 27–8 Ki-67 antigen 52–3 KL-1 144
lactadherin 7
laparoscopy, prostate cancer 88 leuprorelin acetate 90
Lewis Y (Le Y) blood group precursor 53 (table), 57
Light cycler technique 172–4 lineage-specific transcribed genes 2–3 LNCaP cell 93
loss of heterozygocity profiling 22 analysis 32
calculation 33 lymph nodes
breast cancer
axillary, prognostic factor 75, 77 histopathological examination, routine 77 micrometastases, detection 71–81 occult metastatic cells, prognostic relevance
49–50
spread, breast negative disease 67, 77 colorectal cancer 141–4
gastric carcinoma 148
gastrointestinal carcinoma, spread 139 head and neck cancer
locoregional control 20 metastases, distant 20–1
non-small cell lung carcinoma, tumour cell detection 118–21
pancreatic carcinoma 155, 160 lymphoma, progenitor cells 76 LymphoPrep 91
MAGE gene 172, 174–5
magnetic resonance imaging (MRI), tumour staging 21
MALDI-TOF mass spectrometry 25 malignant melanoma see melanoma mammoglobulin 4, 69
breast cancer, early metastatic disease 69
marker genes, melanoma 174–7 melanA/MART-1 172 melanocytes 171 melanoma 171–8
marker genes 174–7 patients, clinical data
clinical cross-sectional analysis 175 marker genes 174–5
PCR data and clinical course 175–7 PCR detection methods
qualitative PCR assay 172–3 real-time PCR assay 173–4 semiquantitative PCR assay 173
melanoma-associated antigen A (MAGE-A) 172, 174–5
MHC class I antigen 52, 53 (table) micrometastases
breast cancer 67–81
esophageal carcinoma, immunocytochemical detection 129–30
microsatellites
fields detection 31–4
genetic alterations, detection 31–4 instability 32–3
minimal residual cancer 1, 19 head and neck 23 monoclonal antibodies 34–5
colorectal carcinoma 144 immunohistochemistry 68
non-small cell lung carcinoma 117–24 MUC1-RT-PCR 4, 6
mucin-1 53 (table), 69 mucin(s) 2, 4
mutagen sensitivity profile 22–3
mutant-allele specific amplification (MASA) 24, 28
mutation ligation assay 102
neck dissection 20
neuroblastoma, progenitor cells 76 non-Hodgkin’s lymphoma 1 non-small cell lung cancer 117–24
tumour cell detection bone marrow 121–3 lymph nodes 118–21 non-specific gene expression 12 nucleic acid based assays 101–2 esophageal cancer 127, 133–4 nucleic acids, amplified 19 NycoPrep 91
occult metastases see micrometastases oligonucleotide ligation assay (OLA) 24, 28 oncogenes 31
OncoQuick 91, 98
p120 antigen 52–3 p53 gene 54
mutated 23–5 mutations
identification 25–6
molecular marker, suitability of 26–7 p53 GeneChip assay 25
pancreatic carcinoma 139, 155–60 bone marrow 155
clinical studies 141 lymph nodes 155 peripheral blood 155 peritoneal lavage 160 PART-1 102
peptide nucleic acid (PNA)-mediated amplification of mutated sequences 101–2
peripheral blood
micrometastases detection breast cancer 48, 50–1, 71–81 colorectal cancer 148 gastric carcinoma 151 pancreatic carcinoma 155, 160 peritoneal lavage
colorectal carcinoma 148 gastric carcinoma 151 pancreatic carcinoma 160 peritoneal metastatic seeding 139 Philadelphia-chromosome 2 plakoglobin 53(table), 56 plaque hybridization assay 24–5
turnover cell detection 24–5, 27–8 POINT-EXACCT 24, 28
polymerase chain reaction (PCR) 2
assays, false positive/false negative 2–3 mechanisms leading 5–13
PolymorphRep 91 primary index tumour 21–2 primers 2
progenitor cells 76
proliferating cell nuclear antigen (PCNA) 92 proliferation-associated antigens 52–4 prostasin 96
prostate cancer 87–106 biopsy 88
bone metastases 87 cause of death 88
cell enrichment/isolation 97–9 cells
disseminated 89 heterozygosity 87, 102 microsatellite instability 87, 102 cytogenetic technique 89 detection, methods 91–7
disseminated epithelial/tumour cells, characterisation 100–6 drug targeting 89–90 epidemiology 88–9 hormone dependence 88 immunohistology 89 immunophenotyping 91–2 incidence 88
laparoscopic treatment 88 localised, treatment alternatives 88 metastatic disease, palliative treatment 88–9 monoclonal antibody therapy 90
mononuclear cells density gradient 91 separation 91 mortality rate 88 predictive values 89 radiation therapy 88 sample preparation 91–7
single cell isolation, Seattle experience 102–6 survival rate 88–9
therapy monitoring 89–90 prostate specific antigen (PSA) 69, 87
cytoplasmic marker 91 messenger ribonucleid acid 94
prostate specific antigen reverse transcriptase polymerase chain reaction (PSA RT-PCR) 87, 89–90, 94–7
prostate specific membrane antigen (PSMA) 87, 94
prognosticator 89–90 surface marker 91 prostatectomy, radical 87–8
tumour progression 89 proto-oncogenes 101–2
PSDRI 102 pseudogenes 3
sequences, amplification 5–6 quantitative (real-time) E48 RT-PCR 37–9
real-time PCR
mammoglobin, amplification 12 quantitative amplification 15 radiotherapy, head and neck cancer 20 restriction endonuclease-mediated selection
(REMS-PCR) 28
restriction fragment length polymorphism-PCR 24, 28
reverse transcriptase PCR (RT-PCR) assay 1 breast cancer 4
micrometastases detection 68–71, 78 esophageal cancer 128, 134
melanoma 171–4
prostate cancer 89–90, 93–7, 100 internal/external control 94 sensitivity 2
solid cancer cells 13–14 rolling-circle amplification 28 RSP53 144
saliva, tumour DNA contamination 29 second field tumours 33–4
second primary tumour 21–2 aetiology 22
classification 22 definition 22 development 22
Sentinel lymph node dissection 80–1
single stranded conformation polymorphism-PCR 28–9
squamous cell carcinoma (SCC) antigen 130 Sunbelt Trial 176–8
T (14;18), translocation 2, 14 T (9;22), translocation 2, 14 Taq errors 30
Taq polymerase 30, 33 TaqMan technique 172–3 telomerase activity 87, 101 tissue-specific genes 1, 12 tissue-specific markers 19 TMPRSS-2 102 TNnMm 81
transferrin receptor 53 (table), 54 translocation 31–2
tumour cells
dissemination, early 1 dormancy 53–4 microinvolvement 131
tumour suppressor genes 31, 54, 101–2 tumour-associated cell membrane glycoproteins
48
tumour-associated proteins 1 tumour-specific markers 19 tyrosinase 172, 174–5 tyrosinase gene 171–2
ulcerative colitis 8
ultrasound-guided fine needle aspiration cytology (USgFNAC) 21
neck nodes 37–8
urokinase-plasminogen activator (uPA) receptor 52, 53 (table), 151
uteroglobins 4 Western-blot analysis 7
