Transcript Document
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
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)
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]
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
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)
COMMON TUMOUR
MARKERS IN CLINICAL
PRACTICE
hCGH
(specific)
beta-hCGH dto
CEA
(NS)
AFP
(NS)
Bence-Jones (MM)
Beta-2-M (S)
BTA (Bladder) (S)
CgA (Chromogranin-A)
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)
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
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)
Assessing prognosis in cancer
Differentiating malignant v benign
Predicting / detecting recurrence
Evaluating extent of disease
Targeting localisation & therapy
Short-comings of TM’s
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.