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ROLE OF TUMOUR
MARKERS IN CANCER
MANAGEMENT
PROFESSOR V. K. GOLAKAI
BSc, MD, ChM, FWACS, FICS, DSc(Med)
PRINCESS MARINA HOSPITAL
DEFINITION
Glyco- / lipoproteins produced by:
 malignant cells
 normal cells in response to tumour
 inflammatory cells and tissues
 found in serum, urine, body fluids
 react with man-made antibodies or
 combine with man-made antigens
 cyto- / histo-compatibility reaction to form
 cyto- / histocompatibility complexes
TYPES OF TUMOUR
MARKERS
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Tumour-Associated Proteins (TAP)
Cell membrane receptors
Hormones
Immunoglobulins / Cellular antigens
Polyamines
Protein clusters and fragments
Chromosomal material
Genes (single, clusters)
Genetic material (DNA, RNA, mRNA)
Cell modulators (transducers / suppressors)
Specific Classes of TM’s
 Enzymes (PSA, NSE, VMA, HVA)
 Cell membrane receptors (ER, PR)
 Tumour antigens (CEA, AFP)
 Antibodies (IgA, IgG, IgM, IgD)
 Antigens (p53, ki-62)
CA-specific proteins(CA 19-9, CA 124)
 Gene mutation products (BR CA 1, 2)
Specific Classes of TM’s (2)
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Tissue-specific proteins (PSA, hCGH)
Special hormones (b-hCGH, h-CGH)
Catecholamines (VMA, HVA, ACTH)
Polyamines
Cytoplasmic / Nucleic material (DNA)
Products of cell turn-over (TNF)
Cellular modulators (ki-62, c-erb-2)
WHO CRITERIA (1) [968]
 Important role in evaluation
Role must be well understood
Role must be recognized
Can be tested early
Detects treatment response
WHO CRITERIA (2) [1968]
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Support for test available
Support / treatment beneficial
Benefits greater than side-effects
Screening must be cost-effective
Detect / diagnose malignant disease
Types of test kits
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ELISA Test Kits
Immuno-histochemical kits (ICH)
Polymerase chain reaction (PCR)
Cluster Kits ( All-in-One Kit)
Detects profiles
Patterns
Prototypes
Constellations
METHODS OF ANALYSIS
Expression of single proteins
Expression of multiple proteins
Chip analysis – “All-in-One”
Expression of protein profiles
(Proteonomics)
 Gene methylation at DNA level
 Genes / mutations (Genomics)
 G-scan (genome ID scan)
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COMMON TUMOUR
MARKERS IN CLINICAL
PRACTICE
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hCGH
(specific)
beta-hCGH dto
CEA
(NS)
AFP
(NS)
Bence-Jones (MM)
Beta-2-M (S)
BTA (Bladder) (S)
CgA (Chromogranin-A)
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CA-15-3 (NS)
CA-19-9 (NS)
CA-72-4 (NS)
CA-27.29 (NS)
CA-125
(NS)
ER / PR (Breast)
HER-2 neu (c-erbB-2)
BR CA-1 / BR CA-2
COMMON TUMOUR MARKERS
IN CLINICAL PRACTICE (2)
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LASA-P (S)
NM-22 (S)
PSA (Prostate-S)
PSMA (Prostate-S)
S-100 (Melanoma)
TA-90 (NS)
TgA, IgA, D, G, M
TPA (NS)
 Alk. p’tase (mets)
 Alpha Amylase
SIADH, ACTH, ADH
 GT-II (NS)
 VMA, HVA (S)
 Polyamines (NS)
 Genes (k-ras, ki-62)
 Chromosome (p53)
Clinical uses of TM’s
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Screening populations at risk
Early detection of tumour
Diagnosing and aiding diagnosis
Predicting response to treatment
Monitoring patients with cancer
Clinical uses of TM’s (2)
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Assessing prognosis in cancer
Differentiating malignant v benign
Predicting / detecting recurrence
Evaluating extent of disease
Targeting localisation & therapy
Short-comings of TM’s
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TM’s are not specific enough
TM’s are not sensitive enough
Not produced by cancer cells alone
TM’s are not ideal for evaluating CA
Poor detectors / predictors early CA
Not good enough prognosticators
TM testing hindered by “Hook effect”
NEW FRONTIERS
 Genomics – Gene structure
 Proteonomics – Protn structure
 Pharmacogenomics – Gene-based drugs
structuring and delivery
 G-scan – Human genome mapping
 New treatment modalities
 Individualised treatment modalities
 Early detection of malignant change
 Greater sensitivity and specificity
 Better monitoring and follow-up care
BRAVE NEW SCIENCE
PHARMACOLOY
Protein based drugs
TM
GENETIC REVOLUTION
Antibiotics, antimicrobials
PHARMACO GENETIC TESTS
Gene chips
G scan
PERFECT HEALTH
DISEASE
Stem cell biology
DNA-Genome
PROTEONOMICS
CYTOGENES
REGENERATIVE
MEDICINE
DEATH
PROCREATION
BIRTH
IMORTALITY/LOGNGEVITY
REGENERATIVE
MEDICNE
HUMAN TRAIT ALTERATIONS
GERM-LINE GENOMICS
REGENERATIVE MEDICINE:
BRAVE NEW WORLD
 Instead of cutting flesh with steel and poisoning the body
with chemicals or burning it with radiation;
 Physicians would gently treat the body with nothing but
proteins and cells, seeking to mend like with like.
 Instead of depending only on his knowledge and limited and
erratic skills snf methods;
 Physicians would seek to tap information in the genome and to
exploit the fact that the body’s cells are designed to be a selfmodulating self-assembling system when given proper signals.
 Instead of sending a patient home merely patched up enough
to live with simmering uncured disease or decaying cells;
 The physician would not rest until the damaged tissues were
replaced with ones as good as new, if not better.