Alida Harahap

Department of Clinical Pathology
Faculty of Medicine, University of Indonesia
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TUMOR

HOST
SUBSTANCE

tumor marker

Measurement in blood/body fluid

Determine the presence of tumor.
Differentiate

Tumor
Normal tissue
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An ideal Tumor Marker:
 Specific for a given type of cancer
 Sensitive to detect small tumors for
early diagnosis and screening
Tumor specific marker: -- few
 specific for a single individual tumor
Tumor associated marker: -- most
Found with different tumors
of the same tissue type

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APPLICATION OF TUMOR MARKER DETERMINATION Screening for cancer Diagnosing for cancer Prognosis for cancer Predictioin of therapeutic response Tumor staging Detecting cancer relapse Monitoring of cancer therapy 28 .

Most cancer markers are not specific for a particular tissue. Exception: PSA Marker should be specific. Most of circulating tumor markers are elevated in the late stages. Exception: PSA Screening must have benefit: survival 27 .APPLICATION OF TUMOR MARKER DETERMINATION Screening for cancer Usefulness: limited Marker should be elevated at early disease stage.

APPLICATION OF TUMOR MARKER DETERMINATION Diagnosing for cancer Usefulness: limited Low sensitivity and specificity 26 .

APPLICATION OF TUMOR MARKER DETERMINATION Tumor staging Usefulness: limited Not accurate 25 .

APPLICATION OF TUMOR MARKER DETERMINATION Prognosis for cancer Usefulness: limited Not accurate 24 .

23 . Sometimes tumor marker provide misleading information: relapse occur without tumor marker elevation or tumor marker elevated non-specifically without progressive disease. In certain group of patients. tumor marker are not produced  do not detect relapse.APPLICATION OF Detecting cancer TUMOR MARKER DETERMINATION relapse Usefulness: controversial Therapies for recurrent cancer are not effective at present.

APPLICATION OF TUMOR MARKER DETERMINATION Predictioin of therapeutic response Very view tumor markers have predictive power Steroid hormone receptors  prediction of response to anti-estrogens Her2/neu amplification  prediction of response to Herceptin in breast cancer 22 .

21 .APPLICATION OF TUMOR MARKER DETERMINATION Monitoring of cancer therapy To know if therapy works.

TUMOR MARKERS CLASSIFICATION • extra cellular • cellular • molecular 20 .

19 .Extra cellular tumor markers In blood or body fluid a substances mostly protein with carbohydrate or lipid component produce by:  a tumor itself  or the host in response to a tumor.

Carbohydrates: Ca 19-9.g  HCG 18 . Ca 15-3. Ca 125. Hormones: e.Extra cellular tumor markers Markers produced by tumor: Oncofetal antigen: CEA (carcinoembryonic antigen) AFP (alfa feto protein).

Extra cellular tumor markers oncoprotein In general represent the re-expression of substances produce normally by embryogenically related tissue MARKER NORMAL PRODUCING EMBRYOGENICALLY CLOSELY RELATED stomach. pancreas DISTANTLY RELATED  CEA colon  AFP liver. breast liver 17 . yolk sac colon. pancreas lung  CG placenta germinal tumor lung. liver. stomach.

Extra cellular tumor markers Tumor mediated markers  Acute phase protein e. IL6 & IL6R  Cell destruction e.g: IL2 & IL2R.g LDH 16 .g: CRP  Cytokine & receptor e.

g estrogen receptor Morphology of cells  anaplasia DNA ploidy  aneuploidy Cytokinetic  S phase fraction Immunophenotyping Chromosome structure abnormal e.Cellular tumor markers       Hormone receptors e.g philadelphia chromosome (bcr-abl gene) 15 .

Molecular tumor markers • deletion of apc & dcc gene  colorectal ca • mutation of supressor gene brca1 & 2  breast & ovarian ca • mutaion of c – erb b-2  breast ca • mutation of supressor gene p53 14 .

TUMOR MARKERS SCHEDULE • before treatment • before each change of treatment • after treatment 1 – 2 year : monthly at first until value have shown marked decrease then every 3 months 3 – 5 year : twice yearly > 6 year : yearly • if marker value increase  frequent monitoring  2 .4 weeks • if relapse or metastasis is suspected • if staging is repeated 13 .

TUMOR MARKERS Linear increased in 3 consecutive specimen with 3 months interval  recurrance 25% increase level progressive increase  recurrance metastasis 50% decrease level  partial remission 12 .

CARCINOEMBRYONIC ANTIGEN (CEA) Glycoprotein: 40-60% carbohydrate & single polypeptide chain Physological Malignant Benign < 10 ng/ml Commnets gastrointestinal mucosa & pancreas during embryonic & fetal life colorectal ca. pancreatic ca inflammatory disease of liver. lung & multiple metastases 11 . breast ca. gastric ca. gi tract & lung pancreatitis. smoker excellent marker for hematogenic metastases particularly in bone. bronchial ca. liver.

atresia oesophagus  in relative risk of down synd 10 . anencephaly. yolk sac hepatocellular ca.ALFA FETO PROTEIN (AFP) Glycoprotein: 4% carbohydrate Physological Malignant Benign < 300 iu/ml Indication fetal liver. germ cells tumor liver diseases. gi tract. pregnancy monitoring pregnancy  in spina bifida.

small intestine. colorectal ca. ca of biliary tract liver & biliary tract diseases pancreatitis marker of second choice in colorectal ca 9 . liver pancreatic ca. ca of stomach. stomach. pancreas.CARBOHYDRATE ANTIGEN 19-9 (CA 19-9) Glycolipid: comprising 3 sugar units Physological Malignant Benign Comment fetal epithelia of colon.

CARBOHYDRATE ANTIGEN 15-3 (CA 15-3) Glycoprotein Physological epithelia of secretory cells Malignant breast ca. lung ca. ovarian ca ca cervix Benign benign mammary tumors < 50 u/ml benign mammary diseases 8 . gi tumor prostate ca.

CARBOHYDRATE ANTIGEN 125 (CA 125) Glycoprotein Physological normal epithelia of fetal & adult bronchial tract Malignant serous ovarian ca undifferentiated ovarian ca ca of endometrium. gall bladder. liver & pancreas first trimester of pregnancy 7 . ca of neck cervical ca Benign benign ovarian cysts. endometriosis disease of adnexae.

CYTOKERATIN 19 FRAGMENT (CYFRA 21-1) Physological epithelial tissue mainly in lung. Malignant squamous cell lung ca non small cell lung ca adenocarcinoma of lung ovarian ca cervical ca ca of bladder 6 .

NEURON SPECIFIC ENOLASE (NSE) Glycolytic enzyme Physological Malignant neuron & neuroendocrine cells of nervous system erythrocyte & platelet small cell lung ca neuroblastoma leukemia 5 .

SQUAMOUS CARCINOMA (SCC) Glycoprotein Physological Malignant Benign normal squamous epithelia squamous ca of neck squamous ca of lung squamous ca of cervix squamous ca of neck inflammatory lung disease epithelial neoplasia 4 .

transurethral biopsy) urinary retention organ specific but not tumor specific 3 . cytoscopy.PROSTATE SPECIFIC ANTIGEN (PSA) Glycoprotein Belong to acid phosphatase group Physological Malignant Benign Comments excretory duct of prostate prostate ca hypertrophy prostate manipulation of prostate (digital rectal examination. coloscopy.

CALCITONIN Polypeptide Containing 32 amino acids Physological Malignant Comment C cells thyroid medullary ca suitable for screening high risk group 2 .

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