TUMOR MARKERS (TMs)
1- Factors Affecting TMs level
2- Clinical Applications of TMs
3- Methods for Evaluating TMs
4- Ideal TMs
5- Classification of TMs and examples
1
Factors Affecting the level of TMs
1. Number of tumor cells:
size, number of produced cells
2. Rate of synthesis of TMs:
cell cycle phase and differentiation stage
3. Site of synthesis in the cell:
cell membrane (secretory)/ intracellular
4. Blood supply to tumor:
2
Clinical Applications of TMs
1. Screen for disease.
2. Differential diagnosis of asymptomatic patients.
3. Clinical staging.
4. Prognostic indicators for disease progression.
5. Detect recurrence of cancer.
6. Monitoring response to therapy.
3
Methods for Evaluating TMs
Reference values are obtained from healthy
population (n= 120), with sex and age-
matched individuals.
For TMs, using benign patients; as the non-
disease group.
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Cut-off value: upper limit of TM concentration in
healthy individuals or benign disease group.
The chosen cut-off value determines the
sensitivity and specificity of the tumor
marker.
• Sensitivity: test's ability to identify positive
results
• Specificity: test's ability to identify negative
results
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Ideal TMs
1. 100% sensitivity & 100% specificity.
2. Positively correlates with tumor volume.
3. Stable not fluctuating.
4. Easy to measure and inexpensive.
5. Predict recurrence before being clinically
detectable.
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Samples used for TMs estimations
1- Blood, plasma, and Serum.
2- Pleural fluid, ascetic fluid, or
pericardial fluid.
3- Urine.
4- CSF.
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Tumor Markers
Tumor Tumor
Specific Associated Oncofetal
NSE, PSA
AFP, CEA
ALP
Calcitonin
CA19.9
CA15.3
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Antigens
Tumor markers Enzymes
Hormones
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I- Antigens
The oncofetal substances are self components, present in embryo
(fetus), diminish to low levels in adults but reappear in cancer.
1- Carcinoembryonic Antigen (CEA)
A glycoprotein shed into blood reaching very high
levels in colorectal cancer (>5 ng/ml).
Over 50% of persons with colon, gastric, pancreatic
cancer have elevated levels of CEA. GIT
CEA levels may also be less markedly elevated in
ulcerative colitis, pancreatitis, colitis, alcoholism
& heavy smokers.
Clinical application:
• Colorectal cancer; alone or with CA19.9
• Breast cancer: Complementary to CA15.3, MCA.
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2-Alpha-fetoprotein (AFP)
Glycoprotein produced by (cells of fetal yolk sac, liver
and GIT), but decline after birth. It is similar in size
and amino acids composition of serum albumin.
AFP test is primarily used for prenatal diagnosis of spina
bifida (CSF leakage) during embryonic development.
High AFP is associated with liver cancer & may be seen in
non-malignant liver diseases as HBV as well as liver cell
injury.
Clinical application:
1.hepatocellular cancer and biliary neoplasms.
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3- Prostate specific antigen (PSA)
A small glycoprotein with protease activity that is
specific for prostate tissue.
High levels are seen in prostate cancer, benign prostatic
hypertrophy, prostate inflammation, and
transuretheral manipulation.
It is recommended to postpone PSA estimation 7-10
days after transuretheral or trasrectal manipulation
It replaced use of prostatic acid phosphatase (PAP) for
prostate cancer screening because it is far more
sensitive.
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4- CA 15.3 (Cancer Antigen 15-3)
Elevated in metastatic breast cancers from 3-9 months.
Give prognostic information in follow-up.
5- CA 19.9 (Cancer Antigen 19.9)
Confirm diagnosis, detect recurrence and assess therapy in
pancreatic carcinoma.
6- CA 125 and ovarian cancer
For diagnosis and monitoring of ovarian cancer. Elevated
levels of CA-125 are also found in women over 50 years.
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7- Mucinous like carcinoma antigen (MCA)
A glycoprotein. Useful in monitoring
patients with breast cancer & non-
malignant breast diseases. Elevated
levels are found in carcinoma of the
ovary and uterus.
8- Tissue polypeptide antigen (TPA)
Produced by epithelial cells. Elevated in
inflammatory diseases (combination),
pregnancy & cholangiocarcinoma
Used in combination with other more specific
markers:
1. CA 15.3 + TPA + MCA for breast cancer.
2. CA 19.9 + TPA + CEA for GIT cancer.
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3. CA 125 + TPA for ovarian cancer.
II- Enzymes
1- PAP (Prostatic Acid Phosphatase)
A glycoprotein isoenzyme produced by lysosomes of
prostate epithelia into secretions.
Elevated with metastatic prostatic carcinoma, BPH,
prostatitis.
PAP has 5 isoenzymes.
Precautions taken before taking serum samples for PAP
assay:
1. Avoidance of rectal examination, avoidance of
catheter passage 7 days before sampling (false
positive results from squeezing prostate tissue).
2. Avoid constipation.
3. Avoid hemolysed samples (RBCs isoenzyme).
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2- ALP (Alkaline Phosphatase)
For metastatic bone cancer, intra and extrahepatic
obstruction of biliary canaliculi.
Differentiation of ALP elevation due to bone or liver
disease is important.
ALP isoenzyme determination with other serum
enzymes, help distinguish the source of an elevated
ALP:
GGT + ALP liver isoenzyme in liver metastases
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3- TK (Thymidine kinase)
TK high in proliferating cells and tumor cells, but not
in resting cells.
TK is useful marker for predicting prognosis and
monitoring response to therapy in patients with:
1- Non-Hodgkin’s lymphoma.
2- Chronic lymphatic leukemia.
3- Multiple Myeloma.
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4- LDH (Lactate Dehydrogenase)
Useful in assessing liver (LDH5) tumors.
LDH3 levels increase in leukemia and lymphoma, but also
in pernicious anemia.
5- Neuron Specific Enolase (NSE)
Is a glycolytic pathway enzyme found only in brain and
neuroendocrine tissue.
A marker of tumors of the CNS, neuroblastomas and
lung cancer (NSCLC).
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III- Hormones
Ectopic Eutopic
not a natural product of its organ hormone is appropriate to the
tissue of origin
aberrant control of unregulated cancer
preexisting genes de- cell metabolism
repression Insulin production by islet
cell tumor,
ACTH, calcitonin, and ADH Calcitonin by medullary
by lung cancers. PTH by thyroid carcinoma
renal cancer.
catecholamines + urinary
VMA by pheochromocytoma
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1- Human Chorionic Gonadotropin (hCG)
A glycoprotein produced by placenta. Marked
elevation in trophoblastic tumors and
testicular cancers.
Some malignancies cause an increase in alpha
and/or beta hCG subunits. So separate tests
have been developed for alpha and beta hCG,
and most laboratories use these assays as
tumor marker tests.
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2- Steroid hormone receptors as prognostic
TMs
Estrogen Receptor (ER)
ER is a protein found in the nucleus of breast
and uterine tissues.
The level of ER in the tissue is used to
determine whether a person with advanced
breast cancer is likely to respond to estrogen
therapy with tamoxifen, which binds to the
receptors blocking the action of estrogen.
Women who are ER-negative have a greater risk
of recurrence than women who are ER-
positive.
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Progesterone Receptor (PGR)
Persons who test negative for both ER
and PR have less than a 5% chance of
responding to endocrine therapy.
Those who test positive for both markers
have greater chance of tumor shrinkage
when treated with hormone therapy
(endocrine: estrogen or progesterone
blockers). 22
Brain Cancer
Blood Cancer
TK, LDH
CA15.3, MCA
AFP, ALP, LDH
CA19.9
PSA, PAP
Prof. El-Mesallamy HO, 2013 23
