ROLE OF TUMOUR MARKERS IN CANCER MANAGEMENT

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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

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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

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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)

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Specific Classes of TMs

• 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)

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Specific Classes of TMs (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)

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WHO CRITERIA (1) 968

• Important role in evaluation
• Role must be well understood
• Role must be recognized
• Can be tested early
• Detects treatment response

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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

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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

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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

• 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

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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. ptase (mets)
• Alpha Amylase
• SIADH, ACTH, ADH
• GT-II (NS)
• VMA, HVA (S)
• Polyamines (NS)
• Genes (k-ras, ki-62)
• Chromosome (p53)

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Clinical uses of TMs

• Screening populations at risk
• Early detection of tumour
• Diagnosing and aiding diagnosis
• Predicting response to treatment
• Monitoring patients with cancer

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Clinical uses of TMs (2)

• Assessing prognosis in cancer
• Differentiating malignant v benign
• Predicting / detecting recurrence
• Evaluating extent of disease
• Targeting localisation therapy

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Short-comings of TMs

• TMs are not specific enough
• TMs are not sensitive enough
• Not produced by cancer cells alone
• TMs are not ideal for evaluating CA
• Poor detectors / predictors early CA
• Not good enough prognosticators
• TM testing hindered by Hook effect

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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

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PHARMACOLOY
BRAVE NEW SCIENCE
Protein based drugs
Stem cell biology
GENETIC REVOLUTION
TM
DNA-Genome PROTEONOMICS CYTOGENES
Gene chips G scan
Antibiotics, antimicrobials PHARMACO GENETIC TESTS
PERFECT HEALTH
REGENERATIVE MEDICINE
DEATH
DISEASE
PROCREATION
IMORTALITY/LOGNGEVITY
BIRTH
REGENERATIVE MEDICNE
GERM-LINE GENOMICS
HUMAN TRAIT ALTERATIONS
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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 bodys cells are
  designed to be a self-
• modulating 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.