This is a presentation that discusses the principles of the use of tumour markers in surgical practice. It further discussed the advantages and disadvantages of tumour markers. Finally, the limitations of tumour markers were highlighted.
2. Outline
ā¢ Introduction
ā¢ Historical perspective
ā¢ Characteristic of an ideal tumor marker
ā¢ Uses of tumor marker
ā¢ Classification of tumor marker
ā¢ Principles of tumor marker use
ā¢ Limitation of tumor marker use
ā¢ Conclusion
3. Introduction
ā¢ Tumor markers are substances detected in higher amounts in serum,
urine or tissues of cancer bearing patients.
ā¢ They are (biochemical and gene) products derived from the metabolic
activity of tumors that are abnormally secreted into body fluids
(blood, urine) or expressed on cell surface/tissues of patients with
cancer in quantities larger than that of normal tissues
4. Introduction
ā¢ Produced by the cancer cells or by the body in response to the cancer
cells
ā¢ Tumor-derived: synthesized directly by the malignant cells
ā¢ Tumor-associated: produced by host tissue in response to tumor
invasion or from metabolic changes induced by the tumor
ā¢ Isolated via immunoassay & immunohistochemistry.
5. Historical perspective
ā¢ First TM is Bence Jones protein in 1847
ā¢ Gutman etal in 1938, identified Acid Phosphatase, which is 1st
clinically useful TM
ā¢ Gold & Freedman in 1965, identified CEA in extracts of gut tumor /
fetal gut tissue
ā¢ RB gene, 1st tumor suppressor/biomarker identified
ā¢ John & Brown dev the technique of Radioimmunoassay
6. Characteristics of an ideal tumor marker
ā¢ It must be tumor sensitive
ā¢ It must be tumor specific
ā¢ It must have positive predictive value
ā¢ It must have a low false negative result
ā¢ Present at concentration that responds rapidly to changing tumor
mass.
ā¢ Present at levels that correlates with malignant tissue mass.
ā¢ Estimation must be cheap & reproducible
7. Clinical uses of TM
ā¢ Screening / prevention e.g PSA in prostate
ā¢ Diagnostic
ā¢ Staging
ā¢ Prediction
ā¢ Prognostic
ā¢ Monitoring
ā¢ Therapeutic
ā¢ Research
ā¢ Medicolegal
8. Classification of Tumor markers
ā¢ Proteins, Peptides, Carbohydrate
ā¢ Oncofetal proteins e.g alfa-fetoproteins, CEA
ā¢ Glycoproteins e.g PSA, CA-15.3, CD 117
ā¢ Enzymes e.g ALP, neuron specific enolase
ā¢ Hormones e.g b-hCG, calcitonin
ā¢ Tissue receptors e.g ER, PR,
ā¢ Immunogobulin e.g. Bence Jones protein
ā¢ Genetic/Bio markers e.g. APC, RB, WT, N-myc
10. Principles of TM use
ā¢ Should not be used alone for diagnosis. There must still be
histological diagnosis
ā¢ Result of single test cannot be relied upon. Serial tests must be done
ā¢ The same lab/same kit should preferably be used
ā¢ Tumor markers for monitoring must have been elevated before
therapeutic intervention
ā¢ T1/2 of tumor markers must be considered before interpretation
ā¢ Cost & relevance to the management of the patient must be
considered
11. Limitations of TM use
ā¢ There is no ideal tumor marker
ā¢ Tumor markers alone cannot be used to make diagnosis (due to their
low sensitivity). Additional mode of diagnosis usually needed
ā¢ Overlap between different tumors & markers
ā¢ Normal level doesnāt exclude disease or recurrence: the level of the
tumor marker may be undetected in the early stage of the disease
ā¢ The level may not correlate with the tumor burden
ā¢ Cost & lack of availability of reagents for RIA
12. Specific TM in Surgical practice
ā¢ General Surgery
Breast- CA 15.3, ER,
Colon- CEA, Ca-125,
GIST- c-KIT( CD117)
ā¢ Urology- PSA, b-hCG
ā¢ Paediatric Surgery- alfa-fetoprotein, RB, WT
ā¢ Plastic surgery- HMB 45
ā¢ Neurosurgery- neuron specific enolase(NSE), VMA/HVA
ā¢ Cardiothoracic surgery- e.g NSE
ā¢ Gynae surgery- b-hCG, inhibin, CA-125
13. Conclusion
ā¢ TM are essential in the screening, diagnosis, treatment, monitoring
and prognostication of tumor in surgical practice
ā¢ It is hoped that with the continue expansion in research, discovery of
an ideal TM will serve as a useful tool in the prevention & early
detection of all types of tumors.