بسم الله الرحمن الرحيم. Faculty of Allied Medical Sciences Clinical Immunology & Serology Practice (MLIS 201). Tumor Markers. Prof. Dr. Ezzat M Hassan Prof. of Immunology Med Res Inst, Alex Univ E-mail: [email protected] Objectives. To define tumor markers
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Clinical Immunology & Serology Practice
To define tumor markers
To describe the characters of ideal TM
To know the clinical applications of TM
To know the classification of TM
To know the clinical use of some example of TM
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.
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 is based on:
1- Biochemical structure.
3- Combination of biochemical structure and function.
4- Discovery of oncofetal markers.
1- Oncofetal Proteins
2- Tumor Associated Antigens
4- Hormonal Receptors
8- Carbohydrate Related Antigens
9- Amino Sugar Derivatives
I- Oncofetal proteins
1-Alpha- fetoprotein (AFP)
2-Carcinoembryonic Antigen (CEA)
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
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.
The word "carcinoembryonic" reflects the fact that CEA is produced by some cancers ("carcino-") and by the developing fetus ("-embryonic").
Tumor antigen is a substance produced in tumorcells.
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
Tissue polypeptide antigen
Prostatic specific antigen
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.
The normal range for CA 125 ranges from 0 to 35μg/mL
In pregnancyandnormal menstruation
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.
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
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 range of CA 15.3 is less than 25 u/ml (units/milliliter)
Breast cancer ,
Ovarian, lung and prostate cancer produce CA 15-3
In some non- cancerous conditions, such as benign breast conditions and hepatitis.
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.
CA 19.9 is synthesized by normal cells in pancreatic and bile ducts, gastric and colonic mucosa, bronchial and salivary glands, endometrium, and prostate.
Reference range is 0-55 U/Ml
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
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.
Serial measurements of CA 19-9 may be useful during and following cancer treatment.
Hormones which are used as tumor markers include:
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 .
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
2-ACTH ( adrenal corticotrophic hormone)
ACTH is secreted from the anterior pituitary gland in
response to corticotropin-releasing hormone from the
As a tumor marker
ACTH can be used as atumor marker for pitutary gland tumors and adrenal gland tumors.
1- Prostatic acid phosphatase (PAP)
2- Alkaline phosphatase
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
Normal rangeof serum PAP is 0.2-3.0 ng/ml
The most common causes for abnormal PAP values include :
2-Prostate cancer that has spread outside the prostate
(particularly to bone)
4- Physical stimulation of the prostate
(colonoscopy, prostate examination)
1 - IL-6
2- IL-2 soluble receptor
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 anti-inflammatory cytokine.
Norma range of IL-6 is 3 pg/ml
Elevated level is seen in cases of
Chronic lymphocytic leukeamia ( CLL )
Systemic lupus erythematosus
1-As a tumor marker
IL-6 can be used as a tumor marker for chronic lymphocytic
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
The Clinical Application Tumor MarkersStudy Questions:
Examples and clinical applications of oncofetal tumor markers
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