This document discusses the use of tumor markers in surgical practice. It defines tumor markers as substances present in or produced by a tumor that can be used to detect or monitor the presence of cancer. The document outlines the classification, clinical applications, limitations, and recent trends in the use of tumor markers. It provides examples of specific tumor markers used for various cancer types and recommendations for the optimal use and interpretation of tumor marker levels.

1. DISCUSS THE USE OF TUMOR
MARKERS IN SURGICAL PRACTICE
PRESENTER:
EZEAKU CHIZOWA .0.
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2. OUTLINE
• INTRODUCTION
• CLASSIFICATION
• CLINICAL APPLICATIONS
• SPECIFIC EXAMPLES
• LIMITATIONS
• RECOMMENDATIONS
• INTERPRETATION
• LOCAL CHALLENGES
• RECENT TRENDS
• CONCLUSION
• REFERENCES
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3. INTRODUCTION
• Tumor markers are substances present in, or produced by, a
tumor itself or produced by host in response to a tumor that
can be used to differentiate a tumor from normal tissue or to
determine the presence of a tumor based on measurements
in blood or secretions.
• A molecule, a process or a substance that is altered
quantitatively or qualitatively in precancerous or cancerous
conditions, the alteration being detectable by an assay.
• Biochemical indicators of the presence of a tumor.
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4. Historical perceptive
• First known attempt to find markers for malignancy was
made 2000 years ago (Egyptian papyrus)
• 1st tumor marker: Bence-Jones protein (1864)
• 1st clinical useful Tumor marker: Acid phosphatase; identified
in 1938 by Gutman et al
• 1965 Gold and Freedman; identified CEA(1st tumor antigen)
• RB gene, 1st oncogene identified
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5. Definition of terms
• Sensitivity is a measure of how commonly a tumor marker
level is elevated in the presence of that particular tumor.
• Specificity measures the proportion of patients without tumor
who have normal marker levels, and are therefore the true
negatives.
• The positive predictive value is the percentage of positive
results (i.e. elevated marker levels) which are true positives.
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6. Ideal tumor marker
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7. Molecular basis of tumor markers
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LEVEL OF
CLASSIFICATION
EXAMPLES
Native protein
PSA in prostate cancer, CEA in colonic
DNA EPIGENETICS Promoter Hyper-methylation, e.g., GSP1, DAP in lung
cancer; p15, p16 in liver cancer
Endogenous Mutations, e.g., NADH dehydrogenase 4
Oncogene Mutation, e.g., K-ras in pancreatic cancer; micro-satellite
alterations in head and neck cancers
Exogenous viral EBV in NPC, Burkitt′s lymphoma; HPV in cervical cancer
Cell based
Endogenous(RNA)
PSA mRNA in prostate cancer, cytokeratin 20 mRNA in breast
cancer
Cell free exogenous
(mRNA) Circulating mRNA, e.g., Tyrosinase mRNA in melanoma

8. Methods of detection
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9. CLASSIFICATION
CATEGORY SUB CATEGORY EXAMPLES
Oncofetal antigens AFP, CEA
Hormones Catecholamines, cacitonin
β-hCG
Glycoproteins CA 125, CA 15-3, CA19-9,
Metabolites VMA, HIAA
Tumour associated markers Proteins Ig, β-2M
Enzymes LDH, Alk phosp, Pteridines
Acute phase proteins CRP, ferritin
Inflammatory markers ESR, viscosity
Ultrastructural
components
Intermediate filament
components
Desmin, vimentin
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10. Classification-contd
Tumor associated
antigens
MHC- related
antigens
H-2 k Antigen
Enzymes PAP, NSE, PLAP
Oncogene products C-myc, c-erbB2
Cytogenetic
products
Philadephia
chromosome
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11. Clinical applications
• Screening and early detection
• Diagnostic confirmation
• Prognosis
• Prediction of therapeutic response
• Monitoring disease and reoccurrence
• Others(localisation, volume estimation, direction for
immunotherapy, clinical staging)
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12. Specific examples
MALIGNANCY TUMOR MARKERS SUGGESTED ROLES
BREAST CA 15-3, CA 27.29 M, R
ER / PR / Her-2neu R T
COLORECTAL, STOMACH,
PANCREAS
CEA, CA 19-9, CA 50 P, M
GERM CELL TUMOUR AFP,β-hCG D, P, M
LDH, PLAP (Seminoma) P, M
PROSTATE PSA S, M, D, P
THYROID Thyroglobulin S, M
Calcitonin (medullary
carcinoma
S, M, P
CARCINOID 5-HIAA D
HEPATOMA AFP S, D, P, M
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M= monitoring, R= reocurrence, S=screening, P=prognosis, D= diagnosis, RT= response to therapy

13. Specific values
• CEA-Serum levels of less than 2.5 ng/mL are normal; 2.5 to 5.0
ng/mL, borderline;and greater than 5.0 ng/mL, elevated
• CA 19-9)-upper limit of normal for a healthy adult being 37
U/mL
• An absolute AFP concentration of more than 500 ng/mL or
HCG level of more than 1000 ng/mL predicts poor prognosis
• PSA- <4ng/ml…age adjusted PSA
• Upper limit of normal in a healthy nonpregnant adult is 25
ng/mL
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14. Specific examples
• DNA based markers are beginning to have profound influence
clinical practice
– HER2/neu amplification status is now being used to guide
treatment with trastuzumab in breast cancer patients
– In patients with metastatic colorectal cancer KRAS
mutation in codon 12 or13 should not receive anti-EGFR
antibody as part of their treatment
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15. Limitations
• Cannot be construed as primary modality for diagnosis of
cancer, because
– Lack of sufficient specificity
– Lack of adequate sensitivity
– Hook effect
– Ectopic tumour markers
– Methodology
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16. Poor specificity
TUMOR MARKER PRIMARY SECONDARY
AFP Primary HCC Teratomas of ovary & testis
CEA Colorectal cancer Various malignancies
Calcitonin Medullary carcinoma Liver, renal, thyroid cancers
Metanephrines Pheochromocytoma Neuroblastoma,
ganglioneuroma
CA 19-9 Pancreatic and gastric ca Various GIT malignancy
IGF- 1 Pituitary cancers Insulinoma
CA 15-3 Breast cancers Various malignancy
NSE Small cell lung cancer Neuroblastoma, kidney
tumors
Immunoglobulins Multiple myeloma Gammopathies
CA 125 Ovarian cancers Various malignancies
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17. Poor specificity
BENIGN CONDITIONS ASSOCIATED WITH RISE IN TUMOUR MARKERS
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18. Ectopic tumor markers
Due to autonomic expression of unrelated genes, denotes of dedifferentiation, assoc with poorer prognosis
and metastasis
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19. Recommendations
• Combination of tumor markers with other investigations
• Redefining the evaluation criteria for tumor markers eg PSA
volume, velocity and density
• Serial testing(transient rise vs constant and continuous rise)
• Use of multiple tumor markers eg CA 9.9 and CEA in CA
pancreas
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20. Recommendations
• Use of marker with the highest elevation for monitoring
reoccurrence
• Monitoring dependent on initial concentration, half life of
marker and nature of therapy
• Tumor marker kinetics should be factored in
• Patient lifestyle and underlying chronic diseases
• Knowledge of the assay methods
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21. Use of multiple tumor markers
MALIGNANCY MAJOR MARKERS OTHER MARKERS
Breast cancer CA 15-3 CEA, calcitonin, β-hCG, LASA-P,
Prolactin
Pancreatic carcinoma CA 19-9 CA 19-5, CA 50, CA 72-4, CEA, CK-
BB, ADH, ALP, γ-glutamyl
transpeptidase, PAP
Colorectal cancer CEA CA 19-5, CA 19-9, CA 72-4, CK-BB,
NSE
Gastric ca CA 72-4 CA 19-9, CA 50, CEA, CK-BB, β-hCG,
LASA-P,
HCC AFP CEA, ferritin, ALP, γ-glutamyl
transpeptidase
Lymphoma β2M TdT, Ki-67, LASA-P
Prostate carcinoma PSA PAP, ALP, CEA, CK-BB, TPA
Lung cancer NSE ACTH, CK-BB, calcitonin, CA 72-4,
CEA, AFP, ferritin, LASA-P
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22. Interpretation (Working Group on Tumor Marker Criteria)
• Partial remission is defined as a decrease in marker levels by
at least 50%.
• Progressive disease, as an increase in marker levels by at least
25%, on the basis of the concept that tumor load is related to
changes in serum tumor marker levels.
• "a complete remission cannot be determined by tumor marker
levels, but if tumor marker levels are elevated, the clinical
decision of complete remission based on conventional
methods should be considered incorrect unless an explanation
for the presence of an elevated level is given“
• Reoccurence
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23. Local challenges
• Cost
• Shortage of reagents/ equipment
• Power supply
• Paucity of skilled personnel
• Poor screening attitude
• Available markers (PSA) in our center
• Long waiting time
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24. Recent trends
• Epigenetic changes- DNA assay for aberrant methylation are
more easier and sensitive than point mutation, and more
stable than RNA and proteins. Potential applications in early
detection, response to therapy and prognostication.
• Genomics
• Proteomics
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25. Recent trends
• The MammaPrint assay is a multigene assay, using 70 genes,
designed to individualize treatment for patients with either
estrogen receptor–positive or estrogen receptor–negative,
lymph node–negative breast cancer
• Transcriptomics
• RNA-based markers have been identified in the context of
global mRNA expression using high-throughput technologies
• Metabolomics – systematic study of the unique chemical
fingerprint that specific cellular process leave behind.
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26. Conclusion
• Tumor markers usage in surgery has increased tremendously
with rapid identification of new markers
• Albeit, it’s injudicious application is fraught with risk of
improper diagnosis and patient management owing to its
insufficient sensitivity and specificity.
• However newer trends are promising as we await an ideal
tumor marker which can be a substitute for tissue diagnosis.
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27. Thanks for listening
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28. REFERENCES
• Schrohl AS, et al. Tumor markers: From laboratory to clinical
utility. Mol Cell Proteomics. 2003;2:378–87.
• Ribbans WJ etal. :Tumor markers. Clinical surgery in general,
4th edition,2004: pg 302-306
• Al-Fallouji MAR: Tumor markers and cancer screening in
surgery. Post graduate surgery,2nd edition, 1998: pg 224-227
• Immunobiology of cancer and tumour markers. A lecture
delivered by Dr O.O. Soriyan
• Samar S. :Tumor markers in clinical practice: General
principles and guidelines, Indian J Med Paediatr Oncol. 2009
Jan-Mar; 30(1): 1–8
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2902207/
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