Tumor markers in routine practice

1. Tumor Markers In
Routine Practice

2. “Each patient with cancer is different—biologically,
clinically, economically, and socially— and a one-‐size--
‐fits‐all approach to treating cancer is not optimal. As
oncologists, our focus has always been, and must remain,
treating the patient, not the disease. We must each acquire
the skills and make the commitment to do so in the optimal
way”
Dr. Richard Schilsky,
ASCO President, 2008-‐2009

3. What are Tumor Markers？
• Biological substances synthesized and released by cancer
cells themselves or
• Produced by the host in response to the presence of
tumor
• Most tumor markers are proteins
• Detected in a solid tumor, in circulating tumor cells in
peripheral blood, in serum, lymph nodes, in bone
marrow, or in other body fluid (urine, stool, ascites)

4. Definition
• Glyco/lipoproteins produced by:
• malignant cells
• normal cells in response to tumor
• inflammatory cells and tissues
• found in serum, urine, body fluids
• react with man-made antibodies or
• combine with man-made antigens
• cyto/histocompatibility reaction to form
• cyto/histocompatibility complexes

5. Ideal Tumor Marker
• A tumor marker should be present in or produced by tumor
itself.
• A tumor marker should not be present in healthy tissues.
• Plasma level of a tumor marker should be at a minimum level
in healthy subjects and in benign conditions
• A tumor marker should be specific for a tissue, it should have
different immunological properties when it is synthesized in
other tissues.

6. Ideal Tumor Marker
• Plasma level of the tumor marker should be in proportion
to the both size of tumor and activity of tumor.
• Half life of a tumor should not be very long
• A tumor marker should be present in plasma at a
detectable level, eventhough tumor size is very small

7. Various Putative Utilities
• Screening
• To identify early cancer risk
• Diagnosis
• To corroborate the diagnosis
• Staging
• To assess & stratify the risk
• Prognosis
• To predict the outcome

8. Various Putative Utilities
• Localization
• To locate the primary
• Therapy
• To target the therapy
• Surveillance
• To detect recurrence in F-Up
• Monitoring
• To evaluate response to Rx.

9. Types of Tumor 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)

10. Tumor Associated Antigens
• Viral Antigen :
• Viral proteins and glycoproteins
• New antigens produced by virally infected host cells under control of
viral nucleic acid
• Tumor specific antigens :
• Tumor cells develop new antigens specific to their carcinogens
• Tumor specific transplantation antigens :
• Tumor cells express new MHC antigens due to alteration of normally
present MHC antigens

11. Tumor Associated Antigens
• Oncofetal antigens:
• Carcino-embryonic antigens (CEA)
• Normally expressed during fetal life on fetal gut
• Reappearance in adult life: GIT, pancreas, biliary system and cancer
breast
• Alpha fetoprotein:
• Normally expressed in fetal life
• Reappearance in adult life; hepatoma

12. Tumor Products
• Hormones :
• Human Chorionic Gonadotrophins (HCG) are secreted in
Choriocarcinoma, Ovarian Ca;
• Thyroxin is secreted in thyroid cancer
• Enzymes :
• Acid phosphatase in prostate cancer;
• Alkaline phosphatase, lipase and amylase enzymes in
cases of cancer of pancreas

13. Specific Classes of Tumor Markers
• Enzymes (PSA, NSE, VMA, HVA)
• Cell membrane receptors (ER, PR)
• Tumor 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)

14. Specific Classes of Tumor Markers
• 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)

15. How to Detect Tumor Markers?
• ELISA
• Immuno-histochemistry (IHC)
• Polymerase chain reaction (PCR)
• Fluorescence in situ hybridization (FISH)
• Cluster Kits ( All-in-One Kit)
• Detects profiles
• Patterns
• Prototypes
• Constellations

16. 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)

17. Tumor Markers By Cancer Type

18. Tumor Markers By Cancer Type

19. Tumor Markers - Drawbacks
• Cancer heterogeneity
• Lack of Specificity – false positives
• Lack of Sensitivity - false negatives
• Benign diseases - positive CA 125 or CEA
• Smokers have raised CEA
• Normal persons also have small amounts
• Higher levels only with large tumor volume
• Some cancers never have higher levels

20. References
• Ying A, Tumor Marker,
https://www.hkacs.org.hk/uploadimages/download/01
044/Tumour%20Markers.pdf assessed on 17.12.16
• Duffy M, Tumor Markers in Clinical Practice: A Review
Focusing on Common Solid Cancers, Med Princ Pract
2013;22:4–11
• Sturgeon C et al; Use of Tumor Markers in Liver, Bladder,
Cervical, and Gastric Cancers, Laboratory Medicine
Practice Guidelines
• The Promise of Tumor Markers,
http://cisncancer.org/research/new_treatments/tumor_
markers/promise_003.html assessed on 16.10.16

21. Questions