Tumor Markers

1. Dr. K. Selvakumar
M.Sc., M.Phil., Ph.D., MBA(HM).,
Medical Biochemist
Tumor Markers

2. Definition
• Tumor markers are substances, usually proteins, that are produced by the
body in response to cancer growth or by the cancer tissue itself and that
may be detected in blood, urine, or tissue samples.
• Some tumor markers are specific for a particular type of cancer, while
others are seen in several cancer types.

3. • Most of the well-known markers may also be elevated in non-cancerous
conditions. Consequently, tumor markers alone are not diagnostic for
cancer.
• There are well-established tumor markers that are routinely used. Many
other potential markers are still being researched.
• Some markers cause great excitement when they are first discovered but,
upon further investigation, prove to be no more useful than markers
already in use.

4. Classification
Tumor markers can be classified in two groups:
• Cancer-specific markers
• Tissue-specific markers

5. Cancer-specific markers
Related to the presence of certain cancerous tissue
- these markers might not be specific in making a diagnosis
- useful in the follow-up of treated patients
- to describe progress of the disease
- response to treatment
Examples of these markers are CEA, CA19-9, CA125

6. • CEA is used as a tumor marker. An elevated or rising CEA level indicates
cancer progression or recurrence.
• The CEA, test measures the amount of this protein that may appear in the blood
of some people who have certain kinds of cancers, especially cancer of the
large intestine (colon and rectal cancer). It may also be present in people with
cancer of the pancreas, breast, ovary, or lung..
Carcinoembryonic antigen (CEA)

7. Tissue-specific markers
• Related to specific tissues which have developed cancer
• these substances are not specifically related to the tumor, and may be present at elevated
levels when no cancer is present.
• But unlike the previous group, elevated levels point to a specific tissue being at fault
• Examples include PSA, beta-HCG,AFP- L3, and Thyroglobulin

8. Alpha Feto Protein (AFP)
• AFP is a major plasma protein (glycoprotein) produced by the yolk sac and the liver during fetal
development that is thought to be the fetal form of serum albumin.
• AFP is measured in pregnant women through the analysis of maternal blood or amniotic fluid, a
s a screening test for a subset of developmental abnormalities
• -Increased in open neural tube defects and omphalocoele
• -Decreased in Down syndrome

9. It used as a biomarker to detect a subset of tumors in non-pregnant women,
men, and children.
A level above 500 ng/ml of AFP in adults can be indicative of :
• Hepatocellular carcinoma
• Germ cell tumors
• Metastatic cancers of the liver

10. Gene Mutations
• Some people are at a higher risk for particular cancers because they have
inherited a genetic mutation
• While not considered tumor makers, there are tests that look for these mutations
in order to estimate the risk of developing a particular type of cancer
• BRCA1 and BRCA2 are examples of gene mutations
• related to an inherited risk of breast cancer and ovarian cancer

11. USES
• Tumor markers are not diagnostic in
themselves
• Definitive diagnosis of cancer is made by
looking at tissue biopsy specimens under a
microscope.
• However, tumor markers provide information
that can be used to:
1. Screen : PSA testing may be used to
screen for prostate cancer
2. Diagnose : CA-125 for ovarian cancer
3. Stage
4. Determine Prognosis
5. Guide Treatment : Breast cancer patients who are
Her2/neu positive are more likely to respond to
Herceptin treatment
6. Monitor Treatment
7. AFP in a child previously treated for teratoma suggests
relapse with endodermal sinus tumor.
8. Determine Recurrence

12. Prostate Specific Antigen (PSA)
• the only tumor marker to gain wide acceptance as a screening test is
PSA for prostate cancer in men.
• Even with PSA there is continued debate among experts and national or
ganizations over the usefulness of this test for screening asymptomatic
men.
SCREENING TESTS

13. • Other markers are either not specific enough (too many false positive,
leading to expensive and unnecessary follow-up testing) or they are
not elevated early enough in the disease process to be useful for
screening
Other Markers

14. Common Tumor Markers
Currently in Use

15. AFP (Alpha-feto protein)
• CANCERS
• WHAT ELSE?
• WHEN/HOW USED
• USUAL SAMPLE
• Liver, germ cell cancer of ovaries or testes
• Also elevated during pregnancy
• Help diagnose, monitor treatment, and
determine recurrence
• Blood

16. CA 15-3 (Cancer antigen 15-3)
• CANCERS
• WHAT ELSE?
• WHEN/HOW USED
• USUAL SAMPLE
• Breast cancer and lung, ovarian
• Also elevated in benign breast conditions
• Stage disease, monitor treatment, and
determine recurrence
• Blood

17. B2M (Beta-2 microglobulin)
• CANCERS
• WHAT ELSE?
• WHEN/HOW USED
• USUAL SAMPLE
• Multiple myeloma and lymphomas
• Crohn's disease and hepatitis
• Determine prognosis
• Blood

18. CA 19-9 (Cancer antigen 19-9)
• CANCERS
• WHAT ELSE?
• WHEN/HOW USED
• USUAL SAMPLE
• Pancreatic, sometimes colorectal and bileducts
• Pancreatitis and inflammatory bowel disease
• Stage disease, monitor treatment, and determine
recurrence
• Blood

19. CA-125 (Cancer antigen 125)
• CANCERS
• WHAT ELSE?
• WHEN/HOW USED
• USUAL SAMPLE
• Ovarian endometriosis, some other benign diseases
• Help diagnose, monitor treatment, and determine
recurrence
• Blood

20. Calcitonin
• CANCERS
• WHAT ELSE?
• WHEN/HOW USED
• USUAL SAMPLE
• Thyroid medullary carcinoma
• pernicious anemia and thyroiditis
• Help diagnose, monitor treatment, and determine
recurrence
• Blood

21. CEA (Carcinoembryonic antigen)
• CANCERS
• WHAT ELSE?
• WHEN/HOW USED
• USUAL SAMPLE
• Colorectal, lung, breast, thyroid, pancreatic, liver,
cervix, and bladder
• hepatitis, COPD, colitis, pancreatitis, and in cigarette
smokers
• Monitor treatment and determine recurrence
• Blood

22. Chromogranin A (CgA)
• CANCERS
• WHAT ELSE?
• WHEN/HOW USED
• USUAL SAMPLE
• Neuroendocrine tumors (carcinoid tumors, neurobla
stoma)
• May be most sensitive tumor marker for carcinoid
tumors
• To help diagnose and monitor
• Blood

23. hCG (Human chorionic gonadotropin)
• CANCERS
• WHAT ELSE?
• WHEN/HOW USED
• USUAL SAMPLE
• Testicular and trophoblastic disease
• Elevated in pregnancy, testicular failure
• Help diagnose, monitor treatment, and determine
recurrence
• Blood, urine

24. Her-2/neu
• CANCERS
• WHAT ELSE?
• WHEN/HOW USED
• USUAL SAMPLE
• Testicular and trophoblastic disease
• Elevated in pregnancy, testicular failure
• Help diagnose, monitor treatment, and determine
recurrence
• Blood, urine

25. Monoclonal immunoglobulins
• CANCERS
• WHAT ELSE?
• WHEN/HOW USED
• USUAL SAMPLE
• Multiple myeloma and WaldeŶstroŵ’s
macroglobulinemia
• Overproduction of an immunoglobulin or antibody,
usually detected by protein electrophoresis
• Help diagnose, monitor treatment, and determine re
currence
• Blood, urine

26. PSA (Prostate specific antigen), total and free
• CANCERS
• WHAT ELSE?
• WHEN/HOW USED
• USUAL SAMPLE
• Prostate
• benign prostatic hyperplasia, prostatitis and with age
• Screen for and help diagnose, monitor treatment,
and determine recurrence
• Blood

27. Thyroglobulin
• CANCERS
• WHAT ELSE?
• WHEN/HOW USED
• USUAL SAMPLE
• Thyroid
• Used after thyroid is removed to evaluate treatment
• Determine
• Blood

28. OTHER TUMOR MARKERS
LESS WIDELY USED

29. BTA (Bladder tumor antigen)
• CANCERS
• WHAT ELSE?
• WHEN/HOW USED
• USUAL SAMPLE
• Bladder
• Not widely available, but gaining acceptance
• Help diagnose and determine recurrence
• Urine

30. Prostatic acid phosphatase (PAP)
• CANCERS
• WHAT ELSE?
• WHEN/HOW USED
• USUAL SAMPLE
• Ovarian
• No evidence that it is better than CA-125 but may be
useful when combined with it; still being studied
• Help diagnose
• Blood

31. CA 72-4 (Cancer antigen 72-4)
• CANCERS
• WHAT ELSE?
• WHEN/HOW USED
• USUAL SAMPLE
• Metastatic prostate cancer, myeloma, lung cancer
• Not widely used anymore; elevated in prostatitis and
other conditions
• Help diagnose
• Blood