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‫بسم هللا الرحمن الرحيم‬
Faculty of Allied Medical Sciences
Clinical Immunology & Serology Practice
(MLIS 201)
Prof. Dr. Ezzat M Hassan
Prof. of Immunology
Med Res Inst, Alex Univ
E-mail: [email protected]
Objectives
1. To define tumor markers
2. To describe the characters of ideal TM
3. To know the clinical applications of TM
4. To know the classification of TM
5. To know the clinical use of some example of TM
Definition
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Tumor markers are gene products that are produced
in low levels by normal tissues.
They are produced by a tumor in large quantities that
can differentiate tumor from normal tissue or detect
the presence of a tumor with blood testing.
Some tumor markers are specific for a particular type
of cancer, while others are seen in several cancer
types.
Most of the well-known markers may also be
elevated in non-cancerous conditions, so tumor
markers alone are not diagnostic for cancer.
Characteristics of Ideal tumor markers
1- Organ specific and tumor specific (specificity).
2- Correlate with tumor load and activity.
3- Positive only when malignancy is present.
4- Positive early in development of malignancy.
5- Easy to measure in blood
At this time there are no tumor markers that work like this.
Clinical application of tumor markers
1- Screening and early detection of cancer.
2- Diagnosis of cancer.
3- prognosis (outlook) for certain cancer .
4- Detecting the early recurrence of cancer .
5- Assess in differentiation between stages of cancer.
6- Monitor the course of cancer during treatment.
Classification of tumor markers
Classification of tumor markers is based on:
1- Biochemical structure.
2- Function.
3- Combination of biochemical structure and function.
4- Discovery of oncofetal markers.
Classification of tumor markers according to
structure
1- Oncofetal Proteins
2- Tumor Associated Antigens
3- Hormones
4- Hormonal Receptors
5- Enzymes
6- Cytokines
7- Oncogenes
8- Carbohydrate Related Antigens
9- Amino Sugar Derivatives
I- Oncofetal proteins
Examples:
1-Alpha- fetoprotein (AFP)
2-Carcinoembryonic Antigen (CEA)
blood levels of Alpha fetoprotein
1- Normal levels of AFP are usually less than 10 ng/Ml
(nanograms per milliliter).
At birth, normal infants have AFP levels 4 or more times normal
range, decreasing during the first 1-2 years of life.
2- Pysiological increase
The majority of pregnant women having a high concentration of
serum alpha fetoprotein
3- Pathological increase
1- Liver diseases
2- Testicular cancer
3- Ovarian cancer
1-Liver diseases
1-Hepatocellular carcinoma.
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AFP can be helpful in the diagnosis and to monitor the
treatment of hepatocellular carcinoma.
AFP levels of over 4,000 ng/mL are a sign of liver cancer.
AFP is also useful in following the response to treatment for
liver cancer. If the cancer is completely removed with surgery,
the AFP level should go down to normal range . If the level
goes back up again, it often means that the cancer has come
back.
2-Acute and chronic hepatitis
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AFP levels are elevated in acute and chronic hepatitis
above100 ng/mL.
AFP cannot be considered diagnostic of HCC.
2-testicular cancer
AFP levels are higher in certain testicular cancers and is used for
follow-up of these cancers.
3- ovarian cancer
AFP levels are higher in certain rare types of ovarian
cancer called yolk sac tumor or mixed germ cell cancer.
2- Carcinoembryonic Antigen ( CEA)
The word "carcinoembryonic" reflects the fact that CEA
is produced by some cancers ("carcino-") and by the
developing fetus ("-embryonic").
Normal blood levels
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The normal range for CEA in an adult nonsmoker is <2.5 ng/ml
For a smoker is <5.0 ng/ml.
Abnormal levels
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The most frequent cancer which causes an increased
CEA is cancer of the colon and rectum.
Others include cancers of the pancreas, stomach, breast,
lung, and certain types of thyroid and ovarian cancer.
Benign conditions which can elevate CEA include
smoking, inflammatory bowel disease, pancreatitis,
cirrhosis of the liver
II- Tumor antigens
Tumor antigen is a substance produced in tumor cells.
Classification of Tumor Antigens
1- Tumor-Specific Antigens, which are present only on tumor
cells and not on any other cell
2- Tumor-Associated Antigens, which are present on some
tumor cells and also some normal cells
Examples of tumor antigens
CA125
CA 15.3
CA 19.9
Tissue polypeptide antigen
Prostatic specific antigen
1- Cancer Antigen 125 (CA 125)
It is a protein that can be made by ovary cells.
If it is present in high levels in the blood or in other
body fluids or tissues, it may be a sign of ovarian
cancer.
Normal levels
The normal range for CA 125 ranges from 0 to 35μg/mL
Abnormal level
1-Physiological
In pregnancy and normal menstruation
2-Pathologicalical
Pathological conditions include: ovarian cancer & other diseases of
the ovary
In addition to any benign and malignant conditions originating in
the endometrium, lungs, breast and gastro intestinal tract.
Clinical value
1- As tumor marker
Not used to screen for ovarian cancer because it is non-specific.
The key problems in using the CA-125 test as a screening tool are
its lack of sensitivity and its inability to detect early stage
cancers.
2- Monitor therapy during treatment for ovarian cancer
It is especially useful for detecting the recurrence of ovarian
cancer
2-Cancer Antigen 15.3 ( CA 15.3)
CA 15.3 is a protein that is a normal product of breast tissue, and
it does not cause breast cancer.
Levels of CA 15-3 increase in breast cancer
In patients with localized breast cancer (cancer limited to the
breast) only about 30% will have increased levels of CA 15-3.
In patients with metastatic breast cancer , CA 15-3 can be found
in 50 to 90% of all cases.
Normal levels
Normal range of CA 15.3 is less than 25 u/ml (units/milliliter)
Abnormal levels
Breast cancer ,
Ovarian, lung and prostate cancer produce CA 15-3
In some non- cancerous conditions, such as benign breast
conditions and hepatitis.
Clinical value of CA 15.3
1-As tumor marker
CA 15.3 is a tumor marker specific for breast cancer.
CA 15.3 is not very sensitive in detecting early breast cancer ;
only 5 to 30% of patients with stage I and II cancer have
elevated levels.
2- Monitor therapy during treatment for breast
cancer
The main use of CA 15.3 is in the follow up of patients with
diagnosed Breast cancer
CA 15.3 is used to monitor patients post-operatively for recurrent
breast cancer.
3- Cancer Antigen 19.9 ( CA 19.9)
CA 19.9 is synthesized by normal cells in
pancreatic and bile ducts, gastric and colonic
mucosa, bronchial and salivary glands,
endometrium, and prostate.
Normal level
Reference range is 0-55 U/Ml
Abnormal level
Abnormal levels can be seen in:
Pancreatic cancer, bile duct cancers ,gastric
cancers, colon cancers, esophageal cancers,
Hepatomas ,non-gastrointestinal tract cancers,
cirrhosis and acute cholangitis
Clinical value of CA 19.9
1-As tumor marker
It is used in patients with pancreatic cancer.
Still, it is the best tumor marker for following patients with
pancreatic cancer.
CA 19-9 can also be used to watch colorectal cancer, but the CEA
test is preferred for this type of cancer.
2- Monitor therapy during treatment for
pancreatic cancer
Serial measurements of CA 19-9 may be useful during and
following cancer treatment.
3-Hormones
Hormones which are used as tumor markers include:
1-B-HCG
2-ACTH
3-Calcitonin
4-Insulin
5-Estrogen
6-Prolactin
1- BHCG
( Human chorionic gonadotropin hormone )
It is a hormone produced by the placenta
Normal ranges of BHCG
1-For female :
The following is a list of serum hCG levels.
3 weeks since LMP: 5-50 mIU/ml
4 weeks since LMP: 3-426 mIU/ml
5 weeks since LMP: 18-7340 mIU/ml
6 weeks since LMP: 1080-56500 mIU/ml
7-8 weeks since LMP: 7650-229000 mIU/ml
9-12 weeks since LMP: 25700-228000 mIU/ml
13-16 weeks since LMP: 13300-254000 mIU/ml
17-24 weeks since LMP: 4060-165400 mIU/ml
25-40 weeks since LMP: 3640-117000mIU/ml
Non-pregnant females: <0.5 mIU/ml
Postmenopausal females: <9.5 mIU/ml.
2-For male :
The normal range for men is between 0-5 Iu/ml .
Clinical Value
1-As a tumor marker
B HCG is used as marker of cancers including
choriocarcinoma and germ cell tumors.
A positive result in males can be a test for testicular
Cancer.
2-ACTH ( adrenal corticotrophic hormone)
ACTH is secreted from the anterior pituitary gland in
response to corticotropin-releasing hormone from the
hypothalamus.
Normal level
Am………..20-80 pg/ml
Pm………..10-30 pg/ml
Clinical value
As a tumor marker
ACTH can be used as atumor marker for pitutary gland
tumors and adrenal gland tumors.
5- Enzymes
Examples:
1- Prostatic acid phosphatase (PAP)
2- Alkaline phosphatase
1-Prostatic acid phosphatase (PAP)
prostatic acid phosphatase is an enzyme found in men,
primarily in the prostate gland and semen to determine
the health of the prostate gland.
Prostate dysfunction results in the release of PAP into
the blood
Normal level
Normal range of serum PAP is 0.2-3.0 ng/ml
Abnormal level
The most common causes for abnormal PAP values include :
1-Prostate cancer
2-Prostate cancer that has spread outside the prostate
(particularly to bone)
3- Prostatitis
4- Physical stimulation of the prostate
(colonoscopy, prostate examination)
6-Cytokines
Examples:
1 - IL-6
2- IL-2 soluble receptor
1- Interleukin-6 (IL-6)
IL-6 is secreted by T cells and macrophages to stimulate
immune response to trauma , especially burns or
other tissue damage leading to inflammation.
It acts as both a pro-inflammatory and antiinflammatory cytokine.
Normal level
Norma range of IL-6 is 3 pg/ml
Abnormal level
Elevated level is seen in cases of
Chronic lymphocytic leukeamia ( CLL )
Prostate cancer
Advanced/metastatic cancer
Diabetes
Atherosclerosis
Systemic lupus erythematosus
Rheumatoid arthritis
Clinical value of IL-6
1-As a tumor marker
IL-6 can be used as a tumor marker for chronic lymphocytic
leukemia (CLL)
2- Monitoring treatment
IL-6 can be used in monitoring of treatment.
3- For treatment
There is an interest in developing anti-IL-6 agents as therapy
against many of diseases associated with increase levels of IL-6
STUDY QUESTIONS:
Mention :
The Clinical Application Tumor Markers
Assignment:
Examples and clinical applications of oncofetal tumor markers
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