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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: elgreatlyem@hotmail.com. Objectives. To define tumor markers

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Faculty of Allied Medical Sciences

Clinical Immunology & Serology Practice

(MLIS 201)

slide3

Tumor Markers

Prof. Dr. Ezzat M Hassan

Prof. of Immunology

Med Res Inst, Alex Univ

E-mail: elgreatlyem@hotmail.com

slide4

Objectives

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

slide5

Definition

  • 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.
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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.

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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.

slide8

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.

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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

slide10

I- Oncofetal proteins

Examples:

1-Alpha- fetoprotein (AFP)

2-Carcinoembryonic Antigen (CEA)

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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

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1-Liver diseases

1-Hepatocellular carcinoma.

  • 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.
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2-Acute and chronic hepatitis

  • 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.

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2- Carcinoembryonic Antigen ( CEA)

The word "carcinoembryonic" reflects the fact that CEA is produced by some cancers ("carcino-") and by the developing fetus ("-embryonic").

slide15

Normal blood levels

  • The normal range for CEA in an adult non-smoker is <2.5 ng/ml
  • For a smoker is <5.0 ng/ml.

Abnormal levels

  • 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
slide16

II- Tumor antigens

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

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Examples of tumor antigens

CA125

CA 15.3

CA 19.9

Tissue polypeptide antigen

Prostatic specific antigen

slide18

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.

slide19

Normal levels

The normal range for CA 125 ranges from 0 to 35μg/mL

Abnormal level

1-Physiological

In pregnancyandnormal 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.

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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

slide21

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.

slide22

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.

slide23

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.

slide24

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.

slide25

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

slide26

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.

slide27

3-Hormones

Hormones which are used as tumor markers include:

1-B-HCG

2-ACTH

3-Calcitonin

4-Insulin

5-Estrogen

6-Prolactin

slide28

1- BHCG ( Human chorionic gonadotropin hormone )

It is a hormone produced by the placenta

slide29

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 .

slide30

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.

slide31

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.

slide32

5- Enzymes

Examples:

1- Prostatic acid phosphatase (PAP)

2- Alkaline phosphatase

slide33

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

slide34

Normal level

Normal rangeof 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)

slide35

6-Cytokines

Examples:

1 - IL-6

2- IL-2 soluble receptor

slide36

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 anti-inflammatory cytokine.

slide37

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

slide38

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

Study Questions:
slide40

Assignment:

Examples and clinical applications of oncofetal tumor markers

نورهان مصطفى محمد

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