TUMOR MARKER molekul protein berupa enzim, hormon, dll yang dalam keadaan normal tidak atau sedikit sekali diproduksi oleh sel tubuh suatu molekul atau proses ataupun suatu substansi yang dapat diukur dengan suatu pemeriksaan (assay) baik secara kualitatif maupun kuantitatif pada kondisi prakanker dan kanker perubahan kadar dapat disebabkan oleh : tumor / jaringan normal sebagai respon terhadap tumor dapat berupa : DNA, mRNA, protein, atau bagian dari protein (seperti proses dari proliferasi, angiogenesis, apoptosis, dan lainnya) bahan untuk pemeriksaan : dapat dideteksi di solid tumor, di circulating tumor cells in peripheral blood, bone marrow, dan cairan tubuh (serum, urine, stool, ascites) karakteristik:

- diproduksi secara eksklusif oleh sel kanker -> sebagai respon terhadap pertumbuhan kanker

- tidak secara ekslusif diproduksi oleh sel kanker -> diproduksi sel normal tp pd kanker produksi

cara identifikasi tumor marker :- pada sel : cytochemistry, flow cytometry- pada jaringan : histochemistry, cytosol assay- pada cairan tubuh : darah, urine, CSF, amniotic fluid

fungsi tumor marker :- untuk screening- kalo pasien udah ada gejala -> untuk deteksi dan menentukan DD- kalo pasien udah terdiagnosis kanker -> untuk tentuin staging- untuk prognostic indicator- untuk monitor respon terhadap terapi- prediksi dari therapeutic response- detect recurrence dari kanker

types of tumor marker :1. tumor specific proteins

hanya diproduksi oleh sel2 tumor/ ganas co/: Philadelphia chromosome in CML, bcr/abl translocation

2. non-specific proteins or markers related to malignant cells diproduksi oleh sel ganas dan sel tubuh lain Oncofetal proteins expressed by cells as they de-differentiate and take on embryonic characteristics co/: AFP, CEA

3. cell-specific proteins over-expresses in malignant cells Proteins expressed normally by differentiated cells, but are expressed at higher rates in the corresponding tumor cells hanya diproduksi oleh 1 jenis sel co/: PSA

Klasifikasi tumor marker :- Protein Onkofetal CEA, AFP- Hormon HCG ,HPL , ACTH , ADH , Parathormon- Enzim PAP , LDH , NSE- Immunoglobulin

- Antigen terassosiasi tumor carbohydrate antigen : CA125, CA19-9, CA15-3, SCC

carcino-associated protein : B2M, PSA, TG, TPA

CEA Complex glycoprotein that is associated with the plasma membrane of tumor cells, from which may be released in the blood protein normally found in the tissue of a developing baby in the womb Blood levels of this protein disappear or become very low after birth In adults, an abnormal amount of CEA may be a sign of cancer. normal values : <2.5 ng/ml in an adult non-smoker & <5.0 ng/ml in a smoker abnormal values :

CEA levels : Breast cancer Cancers of the reproductive and urinary tracts Colon cancer Lung cancer Pancreatic cancer Thyroid cancer

CEA levels also due to:

Cholecystitis Cirrhosis and other liver disease Diverticulitis Heavy smoking Inflammatory bowel diseases (such as ulcerative colitis) Lung infection Pancreatitis Peptic ulcer

B HCG Glycoprotein synthesized by syncythiotrophoblastic cells of normal placenta hormone produced during pregnancy which shows up in the blood test to diagnose pregnancy, and usually becomes positive around the time of the first missed period Serum and urine HCG ↑in early gestation and peak in the first trimester (60~90 days) Ada 2 macam test :1. HCG blood test quantitative :

- Measures the specific level of HCG in blood- helps determine the exact age of the fetus- diagnose abnormal preqnancies : ectopic pregnancies, molar

pregnancies, and possible miscarriages- part of a screening test for Down syndrome- normal results :

HCG level rises rapidly during the first trimester of pregnancy and then slightly declines.

- abnormal results : levels :

Normal pregnancy More than one fetus -- for example, twins or triplet Choriocarcinoma of the uterus Hydatidiform mole of the uterus Ovarian cancer Testicular cancer (in men)

levels : • Fetal death • Incomplete miscarriage• Threatened spontaneous abortion (miscarriage)• ectopic pregnancy

2. HCG blood test qualitative :- checks if there is a hormone called human chorionic gonadotropin in your blood- Normal results : - not pregnant

+ pregnant- Abnormal results :

If your blood HCG is positive and you do not have a pregnancy properly implanted in the uterus, it may indicate:

Miscarriage Ectopic pregnancy Testicular cancer (in men) Trophoblastic tumor Hydatidiform mole Ovarian cancer

PSA glycoprotein enzyme encoded in humans by the KLK3 gene

member of the kallikrein-related peptidase family

secreted by the epithelial cells of the prostate gland

PSA is produced for the ejaculate, where it liquefies semen in the seminal coagulum and allows sperm to swim freely & instrumental in dissolving cervical mucus, allowing the entry of sperm into the uterus.[3]

present in small quantities in the serum of men with healthy prostates, but is often elevated in the presence of prostate cancer or other prostate disorders. normal results:

< 50 thn : < 2, 5 ng/ml & > 50 thn : <5 ng/ml- < 50 thn : < 2,5 ng/ml- 50-59 thn : < 3,5 ng/ml- 60-69 thn : < 4,5 ng/ml

- > 70 thn : < 6,5 ng/ml Abnormal results :

PSA chance of having prostate cancer

In general, the following results need further follow-up and testing:

A PSA of 4 nanograms per milliliter (ng/mL) for most men For men under age 49, levels above 2.5 ng/mL For men aged 50 - 59, levels above 3.5 ng/mL For men aged 60 - 69, levels above 4.5 ng/mL A significant rise from one year to the next may also indicate a higher

risk of having prostate cancer. This is called PSA velocity. A rapidly changing PSA, even within the normal range, raises the

likelihood of cancer.

Other conditions cause PSA :

• A larger prostate• Prostate infection (prostatitis)• Urinary tract infection• Recent tests on your bladder (cystoscopy) or prostate (biopsy)• Catheter tube recently placed into your bladder to drain urine

LDH enzyme that helps produce energy plays an important role in cellular respiration, the process by which glucose (sugar) from food is converted into usable energy for our cells present in almost all of the tissues in the body and becomes elevated in response to cell damage (measured to check for tissue damage) The protein LDH is in many body tissues, especially the heart, liver, kidney, muscles, brain, blood cells, and lungs Normal result : 105-333 IU/L Abnormal result :

Blood flow deficiency (ischemia) Cerebrovascular accident (such as a stroke) Heart attack Hemolytic anemia Infectious mononucleosis Liver disease (for example, hepatitis) Low blood pressure Muscle injury Muscular dystrophy New abnormal tissue formation (usually cancer) Pancreatitis Tissue death

Thyrocalcitonin (Calcitonin) produced by the C cells of thyroid gland that lowers the levels of calcium and phosphate in the blood and promotes the formation of bone

Thyrocalcitonin inhibits bone removal by the osteoclasts and at the same time promotes bone formation by the osteoblasts.

Thyrocalcitonin is given in hypercalcemia (high blood calcium) to lower the calcium level; in osteoporosis to increases bone density and decrease the risk of a fracture; and in Paget disease to decrease bone turnover and bone pain.

Calcitonin test is primarily used to help diagnose : C-cell hyperplasia and medullary thyroid cancer, to evaluate the effectiveness of treatment, and to monitor those affected for recurrence

Calcitonin test also ordered to screen for medullary thyroid cancer in family members of people with multiple endocrine neoplasia type 2 (MEN 2).

Stimulation tests are more sensitive than calcitonin measurements alone. This involves collecting a baseline sample, then giving a person an injection of intravenous calcium or pentagastrin to stimulate calcitonin production. Several more blood samples are then collected over the next few minutes to measure the effect of the stimulation. People with early C-cell hyperplasia and/or medullary thyroid cancer will usually have very significant increases in their levels of calcitonin during this test Normal result : < 10 pg/mL Abnormal result :

level : insulinoma lung cancer medullary carcinoma of thyroid VIPoma

AFP protein normally produced by the liver and yolk sac of a developing baby during pregnancy and decrease soon after birth and has no normal function in adults origin : fetal GI tract, liver , yolk sac, kidney normal values : in males or nonpregnant females <10-20 ng/ml Abnormal results:

AFP :

Cancer in testes, ovaries, biliary (liver secretion) tract, stomach, or pancreas

Cirrhosis of the liver Liver cancer Malignant teratoma Recovery from hepatitis

Abnormal levels of AFP in pregnancy due to:

• Birth defects, including:

- Anencephaly - Duodenal atresia- Gastroschisis - Omphalocele - Spina bifida - Tetralogy of Fallot - Turner syndrome

• Genetic disorders, including Down syndrome• Inaccurate due date• Intrauterine death (usually results in a miscarriage)Multiple pregnancy (twins, triplets, etc.)

In adults, high blood levels (over 500 nanograms/milliliter) of AFP are seen in only three situations:

- HCC

- Germ cell tumors (cancer of the testes and ovaries)

- Metastatic cancer in the liver (originating in other organs)