A

Aberrant crypt foci (ACFs) described, 437

Abl-Bcr proteins and Philadelphia chromosome leukemia, 17 4

Acquired Immunodeficiency Syn­drome (AIDS) and Karposi' s sar­coma, 55

Acute lymphoblastic leukemia/lym­phoma (ALLs)

B-lineage, 202-203, 241 (See also Burkitt's lymphoma)

described, 383-384 genetic abnormalities in, 239-241,

383 hypodiploid, 383 phenotypic/ genotypic correla­

tions, 206 T-lineage,203-204,241

Acute myeloid leukemia (AML) chromosome changes in, 381 c-kit protein in, 239 diagnosis, 204, 235, 380-381 gene fusion products, 205-208,

237- 238 genetic alterations in, 208, 238, 381 prognosis, 381 suppressor genes in, 19 WHO classification, 204, 235

Acute promyelocytic leukemia (APL) described, 205, 235- 237 residual disease, detection of, 237 suppressor genes in, 19 translocations in, 205-208

Adenocarcinoma and COX2, 57 duodenal and ras mutations, 72 gastric and p53, 59 genetic upregulation in metastasis, 309

489

Index

1552S and, 187 and Lewis blood group antigens, 40, 41 and LOH abnormalities, 413 NSCL and c-erbB-2 oncoprotein, 70

Adenomas described, 385- 387, 438 Adenomatous polyposis coli (APC)

as molecular marker, 9, 429-431, 434, 437,438-439

gene in colorectal cancer, 430-431 Adenomatous polyps, 72 Adhesion, association with, 77- 78 a-Fetoprotein (AFP). See also individual

cancer by name characteristics of, 135-136,141,142-143 and disease stage, 145 half life of, 152, 153 in neoplasms, 48 physiologic function of, 38 sensitivity I specificity of, 16, 56-57,

132 Allelic band intensity, detecting, 400,401 Allelic imbalance, assessing, 411 ALLs. See Acute lymphoblastic leuke-

mia/lymphoma (ALLs) Amino acid sequences, predicting, 29 Amphiphysin described, 172 Amplicon defined, 269 Anaplastic lymphoma kinase (ALK)

protein expression, detecting, 250 Aneusomies and FISH detection, 326 Angiogenesis, 76-77, 110, 466 ANNA-l antibody, 172 ANNA-2 protein antibody, 172 Anthracycline therapy, 274, 275 Antibodies and neoplasm diagnosis,

27-28,29 Antigens, 40, 188 Antigen-specific immune responses,

measurement of, 218

490

Anti-nuclear antibodies (ANAs), 169 Anti-Yo/anti-Purkinje cell antibody

(PCA), 172 Apoptosis

association with, 74-76 inducing, 76, 99,466 inhibition of, 57, 71, 75

Artificial neural networks (ANN), 113 Ashkenazi Jews

and APC polymorphisms, 439 breastcancerand,459,460

Assays. See individual assay by name Ataxia telangiectasia (A-T)

breast cancer and, 476 cytogenetics in, 473-47 4 described, 364, 454, 473-475 and DNA repair problems, 361, 364 a-Fetoprotein (AFP) and, 473 immune defects in, 475 probands, haplotypes of, 482 proteins, truncated and, 481 T -cell leukemia and, 47 4-475

Ataxia-telangiectasia mutated (ATM) gene mutations and cancer risk,

475-477,480,481-483 mutation Database url, 481 protein kinase activity assay,

480-481 Autoantibodies, 169-170 Autoimmune diseases, 169 Autoimmunity, 170 Avastatin, 21

B

Basal cell nevus syndrome described, 454

Basic fibroblast growth factor (bFGF) described, 76

Bat-26 as molecular marker, 9 B-cells

clones, detecting, 244-245 lymphornas,214,242-249,384,476

B-cell small lymphocytic lymphoma/ chronic lymphocytic leukemia (CLL), 245, 384, 476

Bel-l protein, 211

Index

Bcl-2 protein, 74, 246 Benign prostate hyperplasia (BPH)

cancer and, 101 finasteride and, 90 and FPSA, 89, 92

Benign PSA, 102 Bevacizumab in cancer therapy, 21 Bioinformatics described, 352 Bladder cancer

and antigen expression, 41 diagnosis and FISH, 95 and EGFR, 71 ligand-receptor assays, PCR based,

349 and LOH abnormalities, 409, 410 NMP marker in, 17,43 p16 gene mutations and, 74 PSMA and, 105 and ras mutations, 72 sPas levels and, 75 and SLN mapping, 297 telomerase activity in, 20

Bladder transitional cell carcinoma and TGF-[3, 69

BLCA-4, sensitivity of, 43 Blm gene, 19 Blood

antigens as tumor markers, 40-42 chromosomal aberrations, detecting,

387-388,397 collection technique, 398-399 gating strategy for, 200 Lewis blood group antigens, 40, 41 and nucleic acid based testing, 94 PCR sampling technique, 398-399 processing/ storage technique,

399-400 rare event detection in, 344

Bloom's syndrome and DNA repair problems,363,364,365

Bone marrow AML, flow cytometry diagram, 205 culture setup technique, 387-388 gating strategy for, 200 and LOH detection, 405

Bone metastases, 91-92

Index

Brain tumors EGFRand, 71 and hnRNP A2/B1 overexpression,

313,314 medulloblastoma, 71, 386 neuroblastoma, 330, 386 andp53, 175 retinoblastoma, 18, 19, 175, 386

BRCA1/BRCA2 gene detection of, 335 gene mutations in, 365,459-461 and hereditary cancer, 18, 19,

458-459 and prostate cancer diagnosis, 98

Breast cancer AFP serum levels in, 48, 136 and anti-CENP-F antibodies, 176 antigen expression and, 41 in Ashkenazi Jews, 459,460 A-T and,476 autoantibody assays in, 108 eDNA microarray of, 341 and c-erbB-2 oncoprotein, 70 and CRP,68 cyclin D1 and, 73 and cyclin E, 73 described, 458-459 detection of, 335, 343,461 E-Cadherin, 77 and EGFR, 70-71 gene amplification in, 263 genetic causes of, 18, 19, 454, 475 HER-2/neu antibodies in, 173 HercepTest kit, 264, 265, 266 and hnRNP A2/B1 expression,

308-309,310,313 IGF and, 71 and LOH, 398, 404-406, 473 lymph node micrometastasis in,

300-301 microsatellite instability (MSI), 60,

405 and monoclonal-defined tumors, 38,

39 mutation carriers and cancer risk,

459

and NMP assays,43 patient management, medical,

461-462 and PNDs, 171 PSMA and, 105

491

and rheumatic syndromes, develop-ment of, 171

RT-PCR and, 299 and sPas levels, 75 sialoglycoproteins and tumor me-

tastasis, 47 in situ hybridization, 266 and SLNs, 287-288, 290-293 staging and SLND, 287 tamoxifen in therapy, 462 telomerase activity in, 20 and topoisomerase Ila 275 VCAM-1, 78

Breast Cancer Prevention Trial (BCPT), 462

Bronchogenic carcinoma, 136 Burkitt's lymphoma. See also Acute

lymphoblastic leukemia/lym­phoma (ALLs), B lineage

described, 212, 214

c

genetic abnormalities in, 248-249, 384

CA 15-3 serological tumor marker, 16, 17,39,46

CA 19-5 serological tumor marker, 40 CA 19-9 serological tumor marker, 16,

39-40, 56-57 CA 50 serological tumor marker, 40 CA 72-4 serological tumor marker, 16,

17 CA 125 serological tumor marker, 16,

39,56-57 Cancer

aggressiveness, predicting, 94 antigens, most w ell-characterized,

191 benign, 136 cells, development of, 3, 53-55, 361,

362, 396

492

detection of (See also Molecular markers in cancer detection)

DNA arrays in, 61, 95, 340 general discussion, 175, 370 immunologic methods, 6, 27, 138 metastatic I recurrent, 148-149 molecular profiling in, 8 p53 gene mutations in, 8-9, 18,

59-60,61,75 proteins arrays and, 61, 348 serologic methods, 6, 16 TRAP, 349

drug targeting, 20-21, 31 hereditary syndromes, features of,

19,453-455 immune responses, identification of,

170-171 modern concepts of, 4 mutation in, 361 predisposition testing

described, 333, 453 flow diagram for, 458 and genetic counseling, 455 informed consent in, 457 results, interpreting, 457-458 risk assessment, 456

and rheumatic disease, 169 specificity, increasing, 89 tissues and hK2, 103

Cancer-associated retinopathy (CAR), 172

Cancer-testis antigens, 177-178 Capillary electrophoresis, 244, 400, 402,

403,416 Carcinoembryonic antigen (CEA)

blood group substance in, 40 identification of, 16, 37-38 sensitivity I specificity of, 16, 56-57

Carcinoembryonic proteins, 37-38 Cathepsin D, 178 Caveolin-1, 108-109 CBF leukemia. See Core binding factor

(CBF) leukemia CCI-779, 21 CD4+ CD56+ malignancies described,

215--216

CD44 alternative splicing regulation,

315-316 described, 78

Index

and prostate cancer diagnosis, 98 eDNA microarrays described, 337, 338,

339,341 Celecoxib and FAP, 466 Cell cycle, 73-74 Cell-free DNA and tumorigenesis

detection, 60-61, 67-68 Cells

growth, 173, 389 lineage specific marker reagents,

establishing, 29 single, analysis of, 350-351 tumor, 110, 289

Cell-specific tumor markers, 43-44, 65-66

CENP-F antigen described, 176 C-erbB-2 gene

in teratoma, 162 and tumorigenesis, 58, 70

Cervical cancer and Hsp-27 antibodies, 178 and LOH abnormalities, 412-413 molecular markers for, 9 molecular pathogenesis of, 396 and sec, 43 sPas levels and, 75 and SLNs, 296

Cervical intraepithelial neoplasia (CIN), 43, 412

Cervical squamous cell carcinoma (CSCC),43

Chemotherapy and anthracycline therapy, 274 resistance and trastuzumab therapy,

273-274 and rheumatic syndromes, develop­

ment of, 171 and tumor marker decline, 152-153,

155-156,160 Children

medulloblastoma, 71, 386 neuroblastoma,330,386

Index

retinoblastoma, 18, 19, 175, 386 Choriocarcinoma

and HCG, 139 incidence of, 130, 131 and LDH, 139, 140 management of, 146

Chromogenic in situ hybridization (CISH),271,330,332,337-340

Chromogranin A (CgA), 44, 66 18q chromosomal allelic loss and prog­

nosis, 440 Chromosomes

aberrations, identifying, 387-388, 397,416

Giemsa banding, 379, 389-390 metaphase, preparation of, 367

Chronic lymphocytic leukemia (CLL), 245,384,476

Chronic myelogenous leukemia (CML), 241-242,382,383

Circulating serum/plasma tumor DNA described, 8

Cisplatin, 274 c-kit protein in AML, 239 Clinical trial assay (CTA) described, 264 Cloning and amino acid sequence pre-

diction, 29 C-myb gene described, 173, 431 C-myc. See Myc family genes Cockayne' s syndrome, 363 Colchicine and mitosis inhibition, 388 Colon cancer

AFP serum levels in, 48 family pedigree showing, 465 genetic causes of, 18, 19, 454 and ICAM-1, 78 and NMP assays, 43 and sFas levels, 75 and VEGF, 77

Colony survival assay described, 368, 477-478,479

Colorectal cancer. See also H ereditary nonpolyposis colorectal cancer (HNPCC) AFP and, 136 APC gene in, 430-431

493

classification, 385, 432, 434, 435 conventional pathway in, 429-432 and COX2, 57 and CRP, 68 development of, 434 DNA Methylator pathway in,

434-436 DNA Mismatch Repair pathway

in,432-434 familial, 438-440 HER-2/neu protein, 431 and IGF, 71 and inflammation, 53 methylation phenotype, 435-436 microsatellite mutation in, 20, 433,

441 molecular markers in, 8-9,396,

440-441 molecular pathogenesis of, 396,

429-430 Myc family genes, 72,431 and p53 mutations, 59, 431 and ras mutations, 72, 408, 435 risk factors for, 294 and SLNs, 294-296 telomerase activity in, 20

Comet assay described, 367 Comparative genomic hybridization

(CGH) described, 251, 333, 396 Compensation defined, 201 Computerized tomography (CT)

and molecular markers, 22, 316 testicular tumors and, 132

Connective tissue tumors described, 385-386

Conventional pathway in colorectal cancer, 429-432

Core binding factor (CBF) leukemia, 237-238

Counterimmunoelectrophoresis (CIE), 6

Cowden syndrome described, 454 COX2. See Cyclooxygenase (COX2) CpG islands (CIMP)and DNA methyla-

tion, 434-435, 438 C-reactive protein (CRP), 53, 68

494

CRP. See C-reactive protein (CRP) CT. See Computerized tomography

(CT) Cyclin D1, 73 Cyclin-dependent kinase inhibitors

(CDKs), 73-74 Cyclin E, 73 Cyclooxygenase (COX2), 57, 68 CYFRA-21 described, 46-47 Cytogenetics

assays described, 367-368 in A-T, 473-474 history of, 379-380 interphase, routine described, 326,

330,333,335 in leukemia, 234-242, 251, 326, 380 metaphase, routine described, 326 molecular, 380

Cytokeratin family and epithelial neo­plasms, 27

Cytokines detection of, 189, 218 and tumorigenesis, 57-58, 69, 70

Cytosolic thymidine kinase (TK1), 47

D

DD3,97 Dendrogram defined, 340 Diagnostic accuracy, improving, 17, 18 Diagnostics testing, world market for,

325,326 Diagnostic testing described, 7 Digital image analysis described,

351-352 Dixon-Moore pathological classification,

testicular germ cell cancers, 130 DNA

arrays and cancer detection, 61, 95,340 changes, testing functional status of,

477 double-stranded breaks (DSBs),

364-366,367,368-369 isolation technique, 400 methylation

CpG islands (CIMP) and, 434-435, 438

Index

transcriptional silencing of genes, 98,395

molecular diagnostic techniques in, 327-328

oncology molecular diagnostics, tar-gets for, 325-336

ploidy analysis described, 216 quantitation of, 400 repairs

deficiency, assays for, 366-370 issues and cancer, 361,363-365,429 mechanisms, 361, 362,364-366

sequence variants of undetermined significance (VUS), 457-458

serum levels and metastatic disease, 397,399

DNA Methylator pathway in colorectal cancer, 434-436

DNA Mismatch Repair pathway in colorectal cancer, 432-434

DNMT encoded methyltransferase and suppressor genes, 19

Double immunodiffusion (DI), 6 Doxorubicin therapy, 275 DRAQ5 described, 216-217 Drugs

efficacy, predicting, 335 NSAIDs, 466 targets, detection tests, 20-21, 31 toxicity, testing, 333, 335

Duodenal adenocarcinoma and ras mutations, 72

Dysgerminoma, 138, 139

E

E-Cadherin, 77, 98 Ectopic tumor markers, 47-49 Effector functions, 188 Embryonal carcinoma

and AFP, 138, 139 HCG and, 138, 139 incidence of, 130, 131 LDH and, 138, 139, 140 management of, 146

Endocytosis described, 262 Endometrial cancer

Index

c-erbB-2 oncoprotein and, 70 and Hsp-27 antibodies, 178 mapping of, 296 and ras mutations, 72 sPas levels and, 75

Enhancer of zone homolog 2 (EZH2) gene

and hereditary cancer, 19 and prostate cancer diagnosis, 97-98,

108 Enzyme immunoassay (EIA) in cancer

detection, 6, 348 Enzyme-linked immunosorbent assay

(ELISA) described, 189, 271 Enzyme-linked immunospot assay

(ELISPOT), 189, 190, 191 Enzymes, 35- 37, 476 Epidermal growth factor (EGFR),

70-71,261 Epithelial tumors described, 385 Epitope Discovery System described, 188 Epitopes

discovery of, 188 software aids for, 188 and tumor markers, 38-39

Epstein-Barr virus (EBV) and Hodgkin's disease, 251 lymphomas, association with, 55, 250 NPCs and, 415, 416

Esophageal cancer p53 and, 59 and sec, 43, 74

Evaluative testing described, 7 EZH2 gene. See Enhancer of zone

homolog 2 (EZH2) gene

F

Familial Adenomatous Polyposis Syn­drome (FAP), 438-439,454, 462, 466

Familial colorectal cancer, 438-440 Family history and cancer diagnosis,

455,456 Fanconi's anemia, 363,364, 365 Fetal tumor antigens. See

Carcinoembryonic proteins

Finasteride, 90, 91 Flow cytometry. See also

Immunophenotyping applications, 217-218 described, 199-201 and MRD detection, 209-210 quality issues in, 201

Fluorescence-activated cell sorter (FACS) analysis and double­stranded breaks (DSBs), 369

Fluorescence in situ hybridization (FISH)

advantages/limitations, 270, 332 aneusomies and, 326

495

and bladder cancer diagnosis, 95 gene amplification, detecting, 330 genetic abnormalities, detecting, 245,

270,326,368,390-391,396 leukemic cells, identification of, 209,

234,241,380 translocations, detecting, 326 and trastuzumab therapy, 272

Follicular lymphoma described, 212 genetic abnormalities in, 246-247,

248,384 Fraction of DNA radioactivity released

(FAR) assay described, 368 Free Prostate Specific Antigen (FPSA).

See also Prostate Specific Antigen (PSA)

benign prostate hyperplasia (BPH), 89,92

and cancer specificity, measuring, 89,92, 100,101

serum components, 102-103 Fusion gene products, 186, 205-208,

236-238

G

Gardner syndrome. See Familial Adenomatous Polyposis Syn­drome (FAP)

Gastric cancer AFP and, 136 and c-erbB-2 oncoprotein, 70

496

E-Cadherin, 77 and ICAM-1, 78 ras mutations and, 72 and sPas levels, 75 SLNs and, 294

Gastrointestinal cancer. See also indi-vidual cancer by name

k-ras mutations in, 72, 408 and LOH abnormalities, 407-409 sialoglycoproteins and tumor

metastasis, 47 telomerase activity in, 20

Gating defined, 200 Genes

abnormalities, detecting, 243, 408 (See also specific technique by name)

amplification, detecting, 330 array technology described,

251-252 cluster analysis of, 340 expression profile, establishing, 370 markers in cancer diagnostics, 18 methylation status, measuring, 344 mutations, 74, 244, 246, 482

(See also individual cancer or gene by name)

rearrangements, detection of, 242-243,336

transcription, suppression of, 434 transcriptional silencing of and DNA

methylation, 98, 395 Genetic counseling described,

455-458 Genitourinary cancer. See also individual

cancer by name and SLN mapping, 296-297

Genomics assays, 370 Germ cell tumors described, 387

(See also individual tumor by name) Giemsa banding, 379, 389-390 Gleevec in cancer therapy, 21, 241, 325,

326 Glycotransferases, 41-42 Gold-facilitated autometallographic in

situ hybridization (GOLDFISH), 271

Index

Gynecological cancers, 296, 410-413. See also individual cancer by name

H

Hairy cell leukemia, 71, 212 Haplotyping and founder mutations,

identifying, 482 Head and neck cancer. See also Squa­

mous cell carcinoma, SCCHN(head and neck SCC)

ATM mutation in, 475 and cyclin D1, 73 and EGFR, 71 field cancerization in, 396 and IL-2, 71-72 and LOH abnormalities, 414, 475 microsatellite mutation in, 20 and sec, 43, 56

Heat antigen retrieval and formalin cross-linking reversal, 29

Heat Shock Protein (Hsp-27), 178 Heliobacter pylori, 54, 55, 59 Hematopoiesis, disruption of, 200, 237 Hepatitis-C, 250 Hepatocellular carcinoma (HCC)

and anti-nuclear antibodies (ANAs), 169

microsatellite mutation in, 20 and mRNA binding proteins,

176-177 p62 overexpression and, 177 and proliferation-associated anti­

gens, 176 virus pathogens and, 55

Hepatoma,75, 141 Hepsin, 96 HER-2/neu protein. See also Herceptin

in colorectal cancer, 431 described, 173-174 and gene amplification detection,

330-331 HER2 protein

detection methods, 271 distribution, 262, 263 immunostain, interpreting, 267-269 overexpression in, 263-270 as prognostic factor, 271-274

Index

receptors amplification status, 265 signaling, 261-262 topoisomerase Ila copy numbers,

275 HercepTest kit

alcohol fixatives and, 268 and breast cancer, 264, 265, 266 scoring methods in, 267

Herceptin in cancer therapy, 21, 70, 90, 105,325,330

Hereditary nonpolyposis colorectal cancer (HNPCC). See also Colorectal cancer

described, 462-463 and DNA repair problems, 361, 429 mutation carriers, risk factors, 464 patient management, medical,

464-465 Heterodimerization defined, 261 Heterogenous nuclear ribonucleopro­

tein. See hnRNP A2 /B1 High-grade prostatic intraepithelial

neoplasia (HGPIN), 106 hnRNP A2/B1

and 703D4, 308 alternative splicing regulation, 315 biology, 309-312 and cancer, 307-309, 310, 313, 314 coding sequence, 313 and E16 silencing, 316 and mRNA transport, regulation of,

314,315 overexpression of, 308, 309, 313 structure/function of, 312- 316

hnRNP proteins, structure/ function, 311

Hodgkin's disease, 78, 251 Homocysteine (Hey), 56, 66-67 Homodimerization defined, 261 Hormones as tumor markers, 35- 37 Host-cell reactivation assay described,

366 HPC1 and prostate cancer diagnosis, 99 HPV. See Human papillomavirus

(HPV) Hsp-27. See Heat Shock Protein (Hsp-

27)

497

hUBF. See Human upstream binding factor (hUBF)

Human chorionic gonadotrophin (HCG)

characteristics of, 136, 141, 142 and disease stage, 145 as tumor marker, 132, 142-144,

152-153 Human immunodeficiency virus type 1

(HIV-1) and E16 silencing, 316 Human papillomavirus (HPV), 54,333,

336 Human upstream binding factor

(hUBF) and RNA transcription, 176

Hybridization data, arrangement of, 340

8 Hydroxy deoxyguanidine (SOH DG) as biomarker, 55

Hyperhomocysteinemia, 56 Hyperplastic polyp s (HPs), 437, 440

I

Identity, establishing cytogenetically, 396

Immune responses, most well charac­terized, 191

Immune suppression and sentinel nodes, 301

Immunoblotting (IB) in cancer detec­tion, 6, 478-480

Immunofluorescence in cancer detec­tion, 6

Immunoglobulin heavy (IgH) gene arrangements, 242, 244, 246

Immunoglobulin light (IgK) gene ar­rangements, 242, 244-245

Immunohistochemistry (IHC), 30, 264, 347

Immunologic methods of cancer detec­tion, 6, 27, 138

Immunomagnetic bead peripheral blood cell capture described, 352

Immunophenotyping. See also Flow cytometry

advantages/limitations, 201-202 and biphenotypic leukemia, 208

498

and diagnosis, 200 Inflammation, 53, 68 Inhibitor of apoptosis protein (lAP)

family described, 106 In situ hybridization

breast cancer and, 266 mRNA detection, 344-345,350

Insulin-like growth factors (IGFs) binding proteins (IGFBPs), 106, 177 described, 71, 106 and malignancy, 59, 71

Intercellular adhesion molecule-1 (ICAM-1)

and metastasis, 78 Interleukin-2 (IL-2) described, 71-72 International Germ Cell Consensus

Classification System (IGCCC) described, 134-135 metastatic germ cell tumors, classify­

ing, 150, 161 International Molecular Epidemiology

Consortium for Ataxia Telang­iectasia (IMECAT), 476

International Union Against Cancer (UICC) TNM staging system, 135

Intracellular cytokine cytometry (ICC), 189-190, 191

Iressa in cancer therapy, 21 Isoenzymes as tumor markers, 35,36

J Juvenile Polyposis Syndrome (JPS), 439

K

Kallikrein, 99-100, 103-104 Karposi' s sarcoma, 55, 250 Karyotype analysis. See Cytogenetics Ki-67 described, 46 Kidney cancer and LOH abnormalities,

409 KLF6 gene and hereditary cancer, 18, 19 Knudson's two-hit hypothesis, 431, 434 KOC antigen, 176- 177 k-ras mutations

and cell-free DNA, 67 in gastrointestinal cancers, 72, 408

L

incidence of, 8, 58, 431 and pancreatic cancer, 9 in SAs, 438

Index

L552S and adenocarcinoma, 187 Laboratory tests, 4-7 Lactate dehydrogenase (LDH)

characteristics of, 136-137, 142-144 in choriocarcinoma, 139, 140 and disease stage, 145, 147- 148 in dysgerminoma, 138 in embryonal carcinoma, 138, 139, 140 LD-1, 137, 138, 139, 141, 142, 150-152 in ovarian carcinoma, 37 in seminoma, 138, 139 in teratoma, 138, 139, 140 in testicular cancer, 132, 133 in yolk sac tumors, 139

Lambert-Eaton syndrome, 172 Laser capture microdissection (LCM)

and angiogenesis, 110 cancer cells, isolating, 95, 111,

350- 351 Leiomyomas described, 385-386 Leucoverin (LV) and tHey, 67 Leukemia. See also individual leukemia

by name acute

diagnosis of, 234 gene fusion products, 236

ATM mutations in, 475 and autoimmunity, 170 biphenotypic, 208 and CD44, 78 cell detection, 204, 209 and CRP, 68 cytogenetic evaluation of, 234-242,

251,380-384 lineage association scoring system,

209,211 LOH in, 475 and metaphase cytogenetics, 326 MLL abnormalities, 238 p16 gene mutations and, 74 and sPas levels, 75 T-cell and A-T, 474-475

Index

Lewis blood group antigen, 40, 41 Li-Fraumeni syndrome

described, 365, 454 and DNA repair problems, 363 Ligand-receptor assays described,

348-349 Limiting dilution analysis (LDA),

188-189, 190 Linkage mapping, 98-99 Lipid-associated sialic acid in the

plasma (LASA-P) described, 47 Lipomas described, 385-386 Liver cancer

and CRP, 68 and ICAM-1, 78 LD-1levels and, 151-152 and TGF-[3, 69

Loss of heterozygosity (LOH). See also individual cancer by name

analysis of, 400-403 described, 395-398 metastasis in, 406 microsatellite markers, analysis, 396 PCR photo in melanoma, 401

Lung cancer and anti-CENP-F antibodies, 176 and antigen expression, 41 deaths from, 307 and hnRNP A2/B1 overexpression, 313 ICAM-1 and, 78 and IGF, 71 imaging technologies and, 22 and LOH abnormalities, 413 MAGE antibodies and, 177- 178 and p53 mutations, 59 PNDs and, 171 and sec, 43 sialoglycoproteins and tumor me­

tastasis, 47 Lung development, mammalian and

hnRNP A2/B1, 308 Lymph nodes

biopsy samples of, 387 mapping,285,286,288,295 metastases and cancer progression,

285,396 micrometastasis in, 299-301, 302

Lymphomas ATM mutations in, 475 and autoimmunity, 170 B-cell

CLL, 245, 384, 476 described, 214 detection of, 242-249 diffuse large, 248

and CRP, 68 cytogenetic evaluation of, 326,

384- 385 diagnosis of, 234, 242-251

499

and Epstein-Barr virus (EBV), 55, 250 Hepatitis-C and, 250 LOH in, 475 mantle cell, 211, 214, 247-248, 384 RT-PCR testing, 342 and sFas levels, 75 T-cell

described, 214 gene rearrangements in, 243,

249-250 translocations in, 235 viruses associated with, 250

Lymphoplasmacytic leukemia, 245-246 Lymphoscintigraphy, value of, 288 Lynch syndrome. See Hereditary

non polyposis colorectal cancer (HNPCC)

Lysophosphatidic acid (LPA), 78 Lytic activity, detecting, 189

M

Magnetic resonance imaging (MRI), 22 Major histocompatibility (MHC) tet-

ramers applications, 192-194 described, 190, 194 peptide binding, characterization of,

188 and prostate cancer diagnosis,

109-110 specificity, conveyance of, 190

MALDI-TOF, 346-347 Mantle cell lymphoma

described, 211, 214 genetic abnormalities in, 247-248,384

500

Marginal zone lymphoma (MZL) described, 212, 214 genetic abnormalities in, 246, 248

Matrix-assisted laser desorption/ion­ization time of flight (MALDI­TOF) described, 346-347

Matrix metalloproteinases (MMPs) described, 68, 106-107 regulation of, 69 and tumor metastasis, 68-69

MDS. See Myelodysplastic syndrome (MDS)

Medulloblastoma, 71,386 Melanoma

cells benign vs metastatic, 293 suspicious features of, 293-294

DNA content, assessing technique, 398-399

and IL-2, 71 and LOH abnormalities, 406-407 lymph node micrometastasis in,

299-300 melastatin loss in, 345 metastases, detecting, 301 microsatellite markers in, 406 molecular pathogenesis of, 396 p16 gene mutations and, 74 p53 gene mutations, 431 pathologic processing of SLNs,

289- 290 and RT-PCR, 297-299 and the SLN, 287 SLN analysis, 291- 292 and TAAs, 186

Melanoma antigen encoding genes (MAGE)

antibodies to and melanoma, 177-178

expression of, 186, 191 and prostate cancer diagnosis, 96,

162 Melastatin described, 344, 345 MEN1 I MEN2, 454 Metaphases, obtaining, 381 Metastasis

and cellular adhesion molecules, 77

Index

and cytokeratin immunostaining, 292

first site of, 286 foci, identifying, 289 and ICAM-1, 78 indications of, 107 LOH and,406 lymph node, 285, 299-301, 302, 396 nodal, 295, 300 process of, 44-45 prostate cancer, 91-92, 107 rejection of, 193 sialoglycoproteins and, 47 skip, 295 and tumor markers, 47, 56, 91-92

MHL. See Tumor markers, half-lives of Microarrays in molecular diagnosis,

338. See also individual microarray by name

Microcapillary electrophoresis de­scribed, 352

Micrometastatic disease, detecting, 88 Microsatellite instability (MSI)

and breast cancer, 60, 405 and colorectal cancer, 20, 433,441 described, 336, 363,432, 463-464 detection of, 366-367, 416 markers of, 9, 55, 437 mismatch repair gene and, 432-434 mutation in, 20, 406, 433, 441 in SAs,438

Minimal residual disease (MRD), 208-209,216

Mismatch repair described, 363-364 Mitosin described, 47 Molecular markers in cancer detection

adenomatous polyposis coli (APC), 9,429-431,434,437,438-439

described, 8-9, 403-404, 408 ethical issues with, 10 imaging diagnostics, 21-22, 316 nonspecific, 45- 47 nucleic acid, 8, 18-20, 95-99 predictive, 29- 31 quality issues with, 9-10

Molecular profiling in cancer detection, 8

Index

Monoclonal antibodies (mAb) and hematological malignancies,

217, 219 immunophenotyping ot 200-201 making,29 astumormarker,38-40,67

Morton-Cochran concept of SLN, 286 mRNA

binding proteins and cancer, 176-177 detection ot 344-345, 350 differential display of, 342 markers,298,417 transport, regulation ot 314, 315

Multiple endocrine neoplasia I/2 (MEN1 / MEN2),454

Multivariate logistic regression (MLR), 113

Myc family genes and adenomatous polyps, 72 autoantibodies to, 173 Burkitt's lymphoma and, 248-249 in colorectal cancer, 72, 431 described, 72 in neuroblastoma, 330

Mycosis fungoids (MF) described, 215 Myelodysplastic syndrome (MDS), 210,

382 Myelomas, multiple, 384

N

Nasopharyngeal cancers (NPCs), 68, 414-416. See also individual cancer by name

Negative predictive value (NPV) de­fined, 5

Neoplasia, classification of, 129 Neoplasms

and amphiphysin, 172 and autoimmune diseases, 169 c-reactive protein (CRP), 53 diagnosis and antibodies, 27- 28, 29 epithelial and cytoskeleton proteins,

27 a -Fetoprotein (AFP) in, 48 formation and mutagenesis, 386 and HCG, 136 and SAGE, 187

501

small cell undifferentiated, 28 spindle celC poorly differentiated, 29 T-cells in, 213, 214 transformation ot 395

Neoplastic hematopathology molecular genetics studies and,

233-244 and the Philadelphia chromosome,

233 Neuroblastoma, 330, 386 Neurological tumors described, 386 Neuron specific enolase (NSE), 44, 66 Nijmegen breakage syndrome (NBS),

363-365 Nodal micrometastasis defined, 299 Non-Hodgkin's Lymphoma

and CD44, 78 cytogenetic evaluation ot 384-385 genetic abnormalities in, 243 phenotypic / genotypic correlations,

214 and rheumatic syndromes, develop­

ment of, 171 and RT-PCR, 342 and sPas levels, 75

Nonsmall cell lung cancer (NSCLC) and hnRNP A2/ B1, 307, 308 markers for, 47 p16 gene mutations and, 74

Nonsteroidal anti-inflammatory drugs (NSAIDs) and apoptosis I angio­genesis, 466

Northern analysis described, 341 NSABP B31 study, 265, 267 NSAIDs and apoptosis/ angiogenesis,

466 NSCL adenocarcinoma and c-erbB-2

oncoprotein, 70 Nuclear matrix protein (NMP), 15, 17,

42-43 Nucleic acid molecular markers, 8,

18-20, 95-99 Nucleic acid sequence based amplifica­

tion (NASBA), 97 Nucleic acid testing (NAT), 94 N ucleosporin protein fusions de­

scribed, 239

502

Nucleotide excision repair (NER) described, 363

0

Oligonucleotides microarrays described, 337, 338

Oncogenes, 15,336 Oncology, 327-329 Oncoproteins as early markers, 58, 70 Oophorectomy, 462 Optical coherence tomography (OCT),

22 Osteosarcoma, 75 Ovarian cancer

AFP and, 136 AFP serum levels in, 48 and antigen expression, 41 CA 125 and, 141 and CD44, 78 c-erbB-2 oncoprotein in, 70 described, 458-459 detection of, 61 epithelial markers, improving, 56 genetic causes of, 18, 19, 454, 475 and LOH abnormalities, 410-412,

475 LPA and, 78 and MAGE antibodies, 177-178 monoclonal-defined tumors and, 38,

39 and PNDs, 171 ras mutations and, 72 and rheumatic syndromes, develop­

ment of, 171 sFas levels and, 75

Oxidative stress and cancer develop­ment, 55

p

p16 gene, 74 p21 gene, 58-59 p27 gene, 19, 74 p53 gene

and angiogenesis, 110 autoantibody (Ab), 75, 174-175,

178-179

and colorectal cancer, 59, 431 described, 74-75, 365

Index

and laboratory testing, 4-5, 162 and LOH abnormalities, 408 mutations in cancer detection, 8-9,

18,59-60,61,75 in SAs,438

p62 antigen, 176-177 p185. See c-erbB-2 P330 antigen described, 176 Paclitaxel resistance and trastuzumab

therapy, 273-274 Pancreatic cancer

AFP and, 48, 136 detection of, 9, 336 development of, 53 and hnRNP A2/B1 overexpression,

309 and ICAM-1, 78 k-ras mutations in, 9 molecular markers in, 396 and monoclonal-defined tumors, 38,

39-40 MRI and,22 and mRNA binding proteins, 177 and ras mutations, 72, 408-409

Pap smear, sensitivity of, 412 Paradoxical deviation defined, 149 Paraneoplastic syndromes (PND),

171-172 Particle agglutination in cancer detec­

tion, 6 Pathogens, known and cancer develop-

ment, 54,55 Pathological diagnosis, basis of, 147 Pathologists, 27-31, 202 Patients, 147-149,460 P AX-5 gene and lymphoplasmacytic

leukemia, 245-246 PCA. See Anti-Yo/anti-Purkinje cell

antibody (PCA) PCNA. See Proliferating cell nuclear

antigen (PCNA) PCR. See Polymerase chain reaction

(PCR) Penile cancer and SLN mapping, 297

Index

Peptide growth factor families, 107 Peptide libraries and vaccine develop­

ment, 188 PET, 22

Peutz-Jegher Syndrome (PJS), 440,454 Pheochromocytoma,44 Philadelphia chromosome

described, 239, 241 discovery of, 379, 382 leukemia and Abl-Bcr proteins, 174 neoplastic hematopathology and,

233 Placental alkaline phosphatase, history

of, 37 Plasma cell disorders and

immunophenotyping, 210-211 Plasma cell myeloma described,

212-213,214 Plasmid assays for DSB repair, 369-370 Polymerase chain reaction (PCR)

blood sampling technique, 398-399 and direct sequencing, 335-336 genetic abnormalities, detecting, 395 and heparin, 398 ligand-receptor assays, 349 LOH, photo of in melanoma, 401

Polymorphisms and prostate cancer diagnosis, 98-99

Positive predictive value (PPV) de­fined,5

Positron emission technology (PET), 22 PPV. See Positive predictive value

(PPV) defined Precursor lesions, 436-438 Predisposition testing

described, 333, 453 flow diagram for, 458 and genetic counseling, 455 informed consent in, 457 results, interpreting, 457-458 risk assessment, 456

Prognosis, predicting, 149-153, 161, 397 Proliferating cell nuclear antigen

(PCNA), 46 Proliferation markers, 46

503

Promoter hypermethylation and pros-tate cancer diagnosis, 98

Prophylactic mastectomy, 462 ProPSA and cancer detection, 101 Prostaglandins and tumorigenesis, 57 Prostate cancer

benign, 102 and c-erbB-2 oncoprotein, 70 classification/ prognosis of, 20 diagnosis of

2DGE,92 artificial neural networks (ANN),

113 BRCA1/BRCA2 gene, 98 Caveolin-1, 108-109 CD44, 98 DD3, 97 E-Cadherin, 98 EZH2 gene, 97-98, 108 general discussion, 85-88, 93 Hepsin, 96 HPC1 and, 99 kallikrein biochemistry and,

99-100 linkage mapping, 98-99 MAGE, 96, 162 MHC tetramers, 109-110 MLR and, 113 NASBA and, 97 polymorphisms in, 98-99 promoter hypermethylation, 98 and protein arrays, 61 proteinsin,99-109, 112-113 SELDI, 92, 112 TRAP, 97

genetic causes of, 18, 19, 475 and IGF, 59, 71 immunotherapy, monitoring, 108 management of, 88 markers

for bone metastases, 91-92 classification of, 87 multiple, methodologies for, 113 neuroendocrine, 109 nucleic acid, 96 proteomics of, 111-113

504

search for, 92-94 and MRI, 22 NMP assays and, 43 and SLN mapping, 296-297 specimen sources for, 94-95 testing milestones, 93

Prostate Cancer Prevention Trial, 90 Prostate gland and human kallikreins,

104 Prostate Specific Antigen (PSA). See

also Free Prostate Specific Antigen (FPSA)

and cancer diagnosis, 3, 15, 56-57, 85,87-88,92

circulating autoantibodies to, 107-108

concentration, 90, 91 Finasteride and, 90, 91 in PSA, 102 intact forms, measuring, 102 limitations of, 100 primary value, goal of, 89 and prostate integrity, 90 sensitivity I specificity of, 16, 17,

100-101 serum, measurement of, 100

Prostate-specific membrane antigen (PSMA), 92, 97, 105

Prostate stem cell antigen (PSCA), 187-188

Prostatic acid phosphate (PAP), 85, 86, 88,92

Prostatin described, 20 Protease as tumor marker, 45 Proteins

arrays and cancer detection, 61, 348 markers, 3, 417 molecular diagnostic techniques in,

328-329,345-348 and prostate cancer diagnosis,

99-109,112-113 RAS, 58- 59, 72, 174 (See also k-ras

mutations) therapeutic targets, predicting, 29 truncated, 348, 481

Protein Truncation Test (PTT), 481

Index

Proteomics assays, 370 PSA-ACT as cancer marker, 100 PTEN mutation and hereditary cancer,

18,19,439 PTT (Protein Truncation Test), 481

Q

Q-PCR, 234,252,380

R

Radioisotopes and lymph drainage, mapping, 285

Radiolabelled in situ hybridization (RISH), 332

RARa gene, 235-236,237 RARb2 gene, 19 RAS protein. See also k-ras mutations;

individual cancer by name autoantibodies of, 174 point mutations, detecting, 336 and tumorigenesis, 58-59, 72

RB gene. See Retinoblastoma Receiver operating characteristic (ROC)

curves, 404, 411 Receptor tyrosine kinases described,

239 Regional node dissection, 285-286 Renal cell cancer

AFP and, 136 and hnRNP A2/ B1 regulation, 314 and LOH abnormalities, 409 PSMA and, 105

Retinoblastoma antibodies to, 175 in children, 386 and hereditary cancer, 18, 19

Retinoic acid receptor (RARb2) gene, 19 Rheumatic syndromes, 169, 171 RNA, molecular diagnostic techniques

in,328,337-345 RNAse L gene and prostate cancer di-

agnosis, 99 RNA transcription, regulation of, 176 ROC curves, 404 Rothmund-Thomson (RecQL4) syn-

drome,365

Index

RT-PCR described, 342 leukemia testing, 234, 238, 252, 342,

380 micrometastases, detection of,

342-343 Philadelphia chromosome and, 241 and PSA, 88 in situ, 298-299, 302 SLNDs, detection of, 342-343 and SLNs, 298, 301 telomerase activity, measuring, 97 tumor classification and, 342 and tumor markers, validating, 95 tyrosinase, 298, 299, 300

RUNX3 gene and hereditary cancer, 19

s Sam68 described, 313 Sarcoma,55,75,250,330,386 Saturated fats and prostate cancer, 90 sec antigen as tumor marker, 66 Schistosoma haematobium, 54 Seminoma

AFP and, 139 detection of, 148, 154, 162 HCG and, 138, 139 incidence of, 130, 131 LDH and, 138, 139 management of, 146

Sensitivity defined, 5, 6, 403 Sentinel lymph node dissection (SLND)

described, 286-287 detection of by RT-PCR, 342-343 diagnostic accuracy in, 288-289, 301 plasma analysis, melanoma, 407

Sentinel lymph nodes (SLN) analysis

immunohistochemical, 292-293 microscopic, 291-292, 293- 294

axillary, localization of, 286 breastcancerand,287-288, 290- 293 described, 286 internal mammary (IMSLN), 288 mapping, 296-297

Morton-Cochran concept, 286 pathologic processing of, 289-291 prognostic significance of, 301

Sequence variants of undetermined significance (VUS), 457-458

Serial analysis of gene expression (SAGE), 187, 342

505

Serological identification of antigens by recombinant expression cloning (SEREX), 171

Serological tumor markers, 16-17, 39-40, 56-57

Serologic methods of cancer detection, 6, 16

Serrated adenomas, 437-438 Serum

applications as tumor markers, 35-37 microsatellite mutation in, 20

Serum tissue polypeptide specific anti-gen (TPS), 46

Sezary syndrome described, 215 sPas described, 75 sFasL described, 76 SG2NA antigen described, 176 Sialic acids described, 47 Sialoglycoproteins and tumor metasta-

sis, 47 Signal transduction described, 261, 262 Signal transduction pathway, associa­

tion with, 69- 72 Single nucleotide polymorphism detec­

tion (SNPs), 333, 335, 417 Single Strand Conformation Polymor­

phism (SSCP), 481 Skinner staging systems for testicular

germ cell cancers, 134, 157 SLN. See Sentinel lymph nodes (SLN) SLND. See Sentinel lymph node dissec­

tion (SLND) Small cell lung cancer (SCLC), 172, 413 SNPs. See Single nucleotide polymor­

phism detection (SNPs) Solid tissue and organ tumors (STOT),

activation of, 385 Southern blotting described, 336 Specificity defined, 5, 6, 403

506

Spectral karyotyping described, 251 S-phase fraction (SPF) described, 216-217 Squamous cell carcinoma (SCC)

described, 43 head and neck SCC (SCCHN) (See

also head and neck cancer) and cell-free DNA, 60-61, 67 cytokine levels and, 57 and LOH abnormalities, 414 p16 gene mutations and, 74 sensitivity/specificity of, 16,17

and p53 mutations, 59 Stomach cancer, 78 Suppressor genes, 18-19,20 Surface-enhanced laser desorption/

ionization (SELDI) and cancer detection, 17-18, 347 and prostate cancer diagnosis, 92, 112

Survivin described, 106

T

T A-4, isolation of, 43 Tamoxifen in breast cancer therapy,

462 T -cell large granular lymphocytic leu­

kemia (T-LDL) described, 213-215 T-cells

antigen-specific, measuring, 185, 218 in A-T, 474-475 CD8+, isolation of, 193-194 enumerating, 109, 190-191, 192-194 lymphomas,214,243,249-250 markers and prostate cancer diagno-

sis, 109 neoplasmsin,213,214 responses, monitoring, 188-191 tumor antigens defined by, 185-186

TCRs and MAGE ligands, 193 Tdt, detection of, 202 Technetium-99 and lymph drainage,

mapping, 285, 289 Telomerase activity

in cancer, 20 as tumor marker, 79,96-97, 105-106

Telomerase repeat amplification proto­col (TRAP), 97, 349

Telomeres, 79, 315

Teratoma and AFP, 138, 139 c-erbB-2 gene in, 162 described, 387 HCG and, 138, 139 incidence of, 130, 131 LDH and, 138, 139, 140

Testicular cancer, 129-131 Testicular germ cell cancers

and AFP, 138

Index

Dixon-Moore pathological classifica­tion, 130

HCG and, 138 histologic types and tumor markers,

137-140 incidence of, 130, 131 monitoring of, 156 nonseminatous, detection of, 148, 154 prepubescent, classification of,

130-131 prognosis/ outcome, 131-132 staging systems of, 133-135

TGF and tumorigenesis, 57-58 Theranostic defined, 90 Therapeutic myelodysplastic syndrome

(tMDS) described, 382 Thrombospondin and angiogenesis,

110 Tissue inhibitors of metalloproteases

(TIMPs), 69, 106-107 Tissue microarrays (TMA) described,

338,340,349-350 TKl. See Cytosolic thymidine kinase

(TK1) Topoisomerase Ila

amplicon, 274-275 and anthracycline chemotherapy, 274 copy numbers vs HER2, 275

TP53 mutation analysis, 335 Transcriptions

profiling and genetic microarrays, 337,339-341

repressing, 235 Transforming growth factor~ (TGF-~),

69 Transient transfection assays, 369 Transitional cell carcinoma (TCC), 43

Index

Translocations, 326 Transmembrane receptors, encoding, 261 Trastumuzab

FDA approval of, 264 NSABP B31 study, 265,267 in therapy, 272, 273

Trichothiodystrophy, 363 T-screening in asymptomatic patients,

140-141 Tumor-associated antigens (TAAs), 185 Tumor markers

blood group antigens as, 40-42 cell-specific, 43-44, 65-66 characteristics of, 3, 17, 135-137,417 clinical applications, 140-145, 160 decline and chemotherapy, 152-153,

155- 156, 160 ectopic described, 47- 49 epitopes and, 38-39 half-lives of, 152-153 human chorionic gonadotrophin

(HCG) as, 132, 142-144, 152-153 isoenzymes as, 35, 36 lysophosphatidic acid (LP A) as, 78 and metastasis, 47, 56, 91-92 monoclonal-defined, 38-40, 67 multiple and diagnostic sensitivity,

154,298 sec antigen as, 66 serological, 16-17,39-40, 56-57 serum,35-37, 132,153-160 stages of, 15, 145-146 telomerase activity as, 79, 96-97,

105-106 types of, 95- 111 usage guidelines, 132- 133, 146,148, 150 validating, 85, 95

Tumor necrosis factor-a (TNF-a) 70, 76 Tumor node metastasis (TNM) guide­

lines, 300 Tumors

antigens discovery of, molecular ap­

proaches, 187- 188 serologically defined, 186-187

in children, incidence, 131 classification and RT-PCR, 342

development of, 53 gene amplification in, 267 Gleevec resistant, 336 isolated cells defined, 300

507

node bed status, predicting, 286-287 solid

culturing of, 388-389 described, 385-387

suppressor genes in detection, 335, 430-431 inactivation of, 434 listing of, 334-335

tolerance induction by, 192 Tumor specific antigens, fluorochrome­

conjugated, 216 Tumor-specific mutated products, 186 Two-dimensional gel electrophoresis

(2DGE), 92 Two-dimensional gel electrophoresis

(2DGE) described, 346 Tyrosine kinase described, 261

u Urine as specimen for cancer testing, 95 Urokinase-type plasminogen activator

(uPA), 107 Urological cancers, 349, 409-410. See

also individual cancer by name Uterine cancer, family pedigree show­

ing, 465 UTMDACC cervical cancer staging

systems for testicular germ cell cancers, 134

v Vaginal cancer and Hsp-27 antibodies, 178 Vascular cell adhesion molecule-1

(VCAM-1), 78 Vascular endothelial growth factor

(VEGF) and angiogenesis, 110 described, 60, 76-77 hnRNP A2/B1 and, 314

Vinyl chloride and serum anti-p53 anti­bodies, 175

Voltage-gated calcium channels (VGCC), 172

508

w Walter staging systems for testicular

germ cell cancers, 134 Werner's syndrome, 363, 364, 365 Western blot analysis described, 346,

478-480 WHO classification

acute leukemias, 202, 208 acute myeloid leukemia (AML), 204,

235 myelodysplastic syndrome (MDS), 210 testicular cancer, 129-130

Women and tumor marker analysis, 56

Index

X

Xeroderma pigmentosa (XP), 361, 363

y

Yolk sac tumors andAFP, 138, 139 described, 387 HCG and, 138 incidence of, 131 and LDH, 139

z Zymogen and cancer, 101