Cancer Biology-Lecture 2.pptx

Cancer Biology Lecture (2) - Tumor Markers Presented by: Dr. Gharieb S. El- Sayyad Associate Professor of Medical Microbiology and Nanotechnology OUTLINE 01 Definition of tumor markers (TM) 0 Clinical importance of ideal tumor...

Cancer Biology Lecture (2) - Tumor Markers Presented by: Dr. Gharieb S. El- Sayyad Associate Professor of Medical Microbiology and Nanotechnology OUTLINE 01 Definition of tumor markers (TM) 0 Clinical importance of ideal tumor 2 0 Properties of ideal tumor markers marker 3 0 Types & classification of tumor 4 markers 0 Examples of some clinically important TM 5  01 Definition of tumor markers 1-Tumor markers (TM): are biologic substances synthesized and released by cancer cells; or produced by the host cells in response to the presence of cancerous 2-Site: Tumor marker may be present in tissue. circulation, in body fluids or associated with cells: TM In the cytoplasm or on cell membrane. 3-Structure: Tumor markers may be enzymes, hormones, and proteins (tumor antigen).  02 Clinical importance of ideal Ideally, tumor marker should provide the following uses in patients having cancer: tumor marker 1. Diagnosis: Screening for the presence of malignancy through symptomatic patients and differentiating malignant from benign conditions. 2. Screening: Knowing the asymptomatic population. 3. Staging: determining the level of the disease, by defining extent of the diseases.  02 Clinical importance of ideal Ideally, tumor marker should provide the following uses in patients having cancer: tumor marker 4. Monitoring: Estimating the response of the therapy. 5. Assessing prognosis: detection of micro- metastasis (malignancy) after curative therapy. 6. Detecting recurrence: early detection of disease recurrence.  03 Properties of ideal tumor markers 1. Have high disease sensitivity i.e. it should be positive in all patients with particular cancer  Sensitivity of any tumor marker refers to the number of true positives, and it could be calculated as follows:  True positive is a malignant case which gives an elevated marker level above the cut-off value.  False negative is a malignant case which gives a normal value for the marker whereas it is proved malignant histo-pathologically.  Cut-off value is the highest value obtained by  03 Properties of ideal tumor markers 2. Have high disease specificity i.e. it should be negative in all normal population.  Specificity of any tumor marker refers to the number of true negatives (normal individuals), and it could be calculated as follows:  True negative is a normal case which gives a normal value for the marker.  False positive is a normal case with elevated marker level above the cut-off value.  Cut-off value is the highest value obtained by the normal control.  03 Properties of ideal tumor markers 3. Its level reflects the stage of the disease. 4. Its level must be stable. i.e. not subjected to marked fluctuation in stable disease state. 5. Organ specific i.e. positive only in certain organ tumor.  Unfortunately, no tumor marker available can fulfill all these criteria for ideal marker.  04 Types & classification of tumor markers A) Types of tumor markers They are divided into 2 types cellular and humoral. Cellular (tissue) tumor markers: – They include antigens located on the cell membrane or intra cellular components as  Humoral (serum) tumor markers: oncogenes. – These are substances, which can be detected in serum. – They are usually synthesized and excreted by tumor cells or released on tumor disintegration or formed as a result  04 Types & classification of tumor markers B) Classification of tumor markers They are divided into 3 classes Hormones, Enzymes, and Tumor antigens.  Hormones: – Example of hormones that are used as tumor markers are: ACTH, ADH, calcitonin,  Enzymes: HCG, PTH, growth hormone and prolactin. – An increase in an enzyme or isoenzymes is not specific or sensitive enough to be used for identifying the type of cancer or the specific organ involvement. – Example of enzymes that are used as tumor markers are: alkaline phosphatase  04 Types & classification of tumor markers B) Classification of tumor markers They are divided into 3 classes Hormones, Enzymes, and Tumor antigens.  Tumor antigens: – They are classified to three sub-classes oncofetal antigens, other tumor antigens,  Oncofetal antigens: and proteins. – These are proteins produced normally during fetal life. – They are present in high concentration in the sera of fetuses and decrease to low levels or disappear after birth. In cancer  04 Types & classification of tumor markers B) Classification of tumor markers They are divided into 3 classes Hormones, Enzymes, and Tumor antigens. Tumor antigens:  Oncofetal antigens: – The production of these proteins demonstrates that certain genes are reactivated as the result of the malignant transformation of cells. – They include carcinoembryonic antigen (CEA) and α-Fetoprotein (AFP).  04 Types & classification of tumor markers B) Classification of tumor markers Tumor antigens:  Other tumor antigens: – Carbohydrate antigen 19.9 (CA 19.9). – Cancer antigen 125 (CA 125). – Cancer antigen 15.3 (CA 15.3). – Cancer antigen 50 (CA 50). – Prostatic specific antigen (PSA). – Tissue polypeptide antigen (TPA).  Proteins: – B2 macroglobulin. – Ferritin.  04 Types & classification of tumor markers B) Classification of tumor markers  05 Examples of some clinically important TM 1.AFP (Alpha feto protein):  Alpha fetoprotein is protein that is produced in early fetal life.  AFP is the major serum protein of human fetus, and it falls to low levels by one year of age.  The cut-off value of AFP is 2-11 ng/ml, but it reaches 500 ng/ml in late pregnancy.  However, elevated levels (more than 500 ng/ml) are found in many cases of hepatocellular carcinoma (hepatoma) and testicular carcinoma.  Furthermore AFP may also be increased in serum of non-neoplastic conditions. In these cases the rise may be transient, and associated with the tissue (usually the liver) response to injury.  05 Examples of some clinically important TM 2. CEA (Carcinoembryonic antigen):  It is a glycoprotein molecule normally found in the tissue of a developing fetus. Levels of CEA in the blood decrease after birth.  CEA is normally found in small amounts in the blood of most healthy people Cut-off value of CEA is about 5 ng/ml.  High CEA levels (above 5 ng/ml) have been found in colonic cancer and in some tumors of the lung, pancreas, uterus, and breast.  Less marked elevations occurs in non-neoplastic diseases such as emphysema, ulcerative colitis,  05 Examples of some clinically important TM 3. CA 19-9 (Carbohydrate antigen 19-9):  Carbohydrate antigen is a protein that is found in very small amounts on the surface of certain cancer cells. It may be found in the blood when it is shed by tumor cells.  It is also found in trace amounts in the pancreas, liver, gall bladder and lungs of healthy adults.  A CA19-9 test may be done to check:  a person’s response to treatment for pancreatic cancer, especially advanced pancreatic cancer. if pancreatic cancer is still growing or has come back (recurred) after treatment.  05 Examples of some clinically important TM 4. CA 125 (Cancer antigen 125):  Cancer antigen 125 is a protein produced by a variety of cells, particularly ovarian cancer cells.  It is found in trace amounts in the pleura, pericardium and peritoneum of healthy adults.  CA 125 is most reliable and highly specific tumor marker for ovarian cancer.  05 Examples of some clinically important TM 5. CA 15.3 (Cancer antigen 15.3):  CA 15.3 is the most reliable and highly specific tumor marker for breast cancer.  The CA15.3 level can provide prognostic information in the follow-up management of patients with breast cancer.  Cut-off value of CA 15.3 is 35 units/ml. 6. CA 50 (Cancer antigen 50):  CA 50 is glycolipid.  Monitoring of the disease and the effectiveness of therapy for carcinoma of the pancreas.  The upper limit of normal CA 50 is 23  05 Examples of some clinically important TM 7. PSA (prostatic specific antigen):  It is widely accepted tumor marker in prostatic cancer.  PSA is glycoprotein produced only by prostatic epithelial cells and it is organ specific.  Elevated Level (more than 4 ng/ml) occurs in:  60% of localized prostatic cancer. 40% of benign prostatic hypertrophy.  Normal level: 0-4 ng/ml.  05 Examples of some clinically important TM 8. PAP (Prostatic acid phosphatase):  One of the famous enzymes used as tumor marker.  The serum level of PAP is elevated in prostatic carcinoma.  Certain precautions must be taken before taking serum samples for PAP assay:  These include avoidance of rectal examination and passage of catheter at least 7 days before sampling. Cut-off value is 0.5-11 units/liter.  05 Examples of some clinically important TM 9. LDH (Lactate dehydrogenase):  An elevation in all five LDH isoenzymes (LDH1, LDH2, LDH3, LDH4 & LDH5) can be seen in leukemia and lymphoma.  Selective increases in LDH isoenzymes LDH3  and LDH5 (liver enzyme) may occur in liver Cut-off value of total LDH ranges from 48 carcinoma. to 115 units/liter. 10. Calcitonin:  Patients with medullary thyroid carcinoma can be screened by measuring calcitonin levels  05 Examples of some clinically important TM 11. HCG (Human chorionic gonadotropin):  Hormone produced by placenta, and used for detection of pregnancy.  Reaching maximum level at 8th week of gestation.  It increases in testicular carcinoma. Dr. Gharieb S. El-Sayyad