Tumor Markers
Noor Ullah
[Link]@[Link]
08/20/2020 1
Tumor markers
• Tumor markers are hormones, enzymes, peptides or proteins abnormally
synthesized and released by the cancer cells, or are produced by the host cells in
response to cancerous growth.
• Tumor markers may be present in the body fluids, blood, cell membranes or in
the cytoplasm of the cells.
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Characteristics of an ideal tumor marker
• Specificity for a single type of cancer
• High sensitivity and specificity for cancerous growth
• Correlation of marker level with tumor size
• Homogeneous (i.e., minimal post-translational modifications)
• Short half-life in circulation
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Roles for tumor markers
• Determine risk (PSA)
• Screen for early cancer (calcitonin, occult blood)
• Diagnose a type of cancer (hCG, catecholamines)
• Estimate prognosis (CA125)
• Predict response to therapy (CA15-3, CA125, PSA, hCG)
• Monitor for disease recurrence or progression (most widely used
function)
• Therapeutic selection (her2/neu, k-ras)
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Types of Tumor Markers
• Hormones (hCG, calcitonin, gastrin, prolactin)
• Enzymes (acid phosphatase, alkaline phosphatase, PSA)
• Cancer antigen proteins & glycoproteins (CA125, CA 15.3, CA19.9)
• Metabolites (norepinephrine, epinephrine)
• Normal proteins (thyroglobulin)
• Oncofetal antigens (CEA, AFP)
• Receptors (ER, PR, EGFR)
• Genetic changes (mutations/translocations, etc.)
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Clinical significance of tumor markers
• Tumor markers are used as diagnostic and prognostic agents.
• They are used for screening of cancer in asymptomatic individuals
• As an adjunct in clinical staging of the cancerous condition
• For monitoring during cancer treatment
• For early detection of recurrence of the cancerous process.
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Techniques of estimation
• Tumor markers can be detected by:
• Immunohistochemistry if they are present on cell membrane or in
cytoplasm of cell.
• Immunochemistry - radioimmune assay: RIA and IRMA
• Enzyme immune assay - ELISA, EIA, MEIA
• Fluorescence assay - FPIA
• Chemiluminescence assay - CMIA
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Classification of tumor markers
• The clinically important tumor markers are as follows-
• 1) Tumor associated antigens- These are also called oncofetal
proteins/antigens.
• The properties of cancer cells are changed and they start producing
abnormal products from the mutated/ altered oncogenes.
• The tumor associated antigens are produced ln large amount ln fetal
life, but after birth these antigens disappear and are present ln very
minute amount ln adults.
• In malignant cells, the synthesis of oncofetal antigens ls reactivated
and their concentration ln blood and cancer cells is increased.
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Examples of oncofetal antigens
• a) Carcinoembryonic antigen (CEA)- Gastrointestinal cancer, ovarian,
breast, cervical and lung cancers , best marker of colorectal carcinoma.
• b) Alpha feto protein (AFP)
• Synthesized by the fetal liver
• Re-expresses in certain types of tumors
• Normally functions as a transport protein and helps to regulate oncotic pressure in
the fetus
• Germ cell (ovaries, testes) tumors and hepatocellular carcinoma
• c) Tissue polypeptide antigen- Colonic cancer, breast and prostatic cancer.
• Other less important antigens are:
• Pancreatic oncofetal antigen, Colon specific antigen, Beta oncofetal antigen
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2. Carbohydrate antigens
• These antigens are more specific ln determining the site of tumor.
• They are organ and tissue specific.
• Examples of important carbohydrate antigens are-
• a) CA-125: Mainly ovarian cancer, but may also be elevated ln
endometrial cancer, fallopian tube cancer, lung cancer, breast cancer
and gastrointestinal cancer.
• b) CA-15-3: Breast cancer
• c) CA-19-9: Mainly pancreatic cancer, but also colorectal cancer and
other types of gastrointestinal cancers.
• d) CA- 27-29: Breast cancer.
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3. Pregnancy associated antigens
• a) Human chorionic gonadotropin- β-subunits- (β-HCG): It ls a
placental hormone, synthesized by the syncytiotrophoblastic cells of
placenta.
• In the non pregnant state it is present only in very minute
concentration in the serum, but it is markedly elevated ln pregnancy.
• The peak value ls attained at 12 weeks of pregnancy, then it declines
slowly to reach 1/5 th of peak at the end of 20 weeks and continues
at a very low level for a few days even after parturition.
• Measurement of HCG in serum and urine ls undertaken to diagnose
pregnancy.
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Pregnancy associated antigens
• Chemically it has two subunits-α and β-subunits.
• The β subunit is typically measured, because of its increased
specificity and because some tumor cells secrete only β subunit.
• Its high level ls an ideal marker of gestational trophoblastic and germ
cell tumors of testes and ovaries.
• Its high level is also observed in Seminoma, embryonal carcinoma,
teratocarcinoma and choriocarcinoma.
• b) Placental like Alkaline phosphatase-(Regan isoenzyme- PLAP)- The
Regan isoenzyme is a placental -type alkaline phosphatase that is
expressed in a number of human tumors, particularly ln gonadal and
urologic cancers.
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Pregnancy associated antigens
• c) Other antigens:
• Human placental lactogen (HPL)
• Sex hormone binding protein (SHBG)
• Steroid binding β globulin (SBBG)
• α2 Pregnancy associated globulin (PAG)
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4. Mammary associated antigens
• MCA (Mucin like carcinoma associated antigen): Breast cancer
• MSA (Mammary serum antigen)- Breast cancer
• MAP(Mitogen activated protein kinase)- Breast cancer
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[Link] used as tumor markers
• ACTH- Lung cancer, Medullary carcinoma of thyroid and pancreatic
carcinoma
• Calcitonin- Medullary carcinoma of thyroid
• Catecholamines- Pheochromocytoma
• Gastrin- Gastrinoma
• Insulin- Insulinoma
• Glucagon- Glucagonoma
• Serotonin Carcinoid syndrome
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6. Enzymes and Isoenzymes used as tumor markers
• a) Lactate dehydrogenase (LDH)
• Total LDH- Lymphoma, leukemia, germ cell tumor, breast and lung cancer
• LDH1- Germ cell tumors, ovarian carcinoma, Osteosarcoma
• LDH 2,3,4- Leukemias
• LDH-5- Hepatoma , breast cancer, colorectal cancer and other benign liver diseases
• b) AIkaIine phosphatase (ALP)
• Liver isoenzyme- Metastatic liver cancer
• Bone isoenzyme- Metastatic bone disease, benign bone disease
• Regan isoenzyme- Lung cancer, ovarian cancer, breast cancer, colonic cancer and
uterine cancer
• Nagao isoenzyme- Metastatic carcinoma of pleural surfaces, adenocarcinoma of
pancreas and bile duct.
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6. Enzymes and Isoenzymes used as tumor markers
• c) Acid phosphatase
• Prostatic acid phosphatase- Prostate cancer
• d) Creatine Kinase
• CPK- BB- Adenocarcinoma, prostatic carcinoma
• e) α1- Antitrypsin- Germ cell tumor of testes and ovaries.
• f) Neuron specific Enolase (NSE)- Neuroblastoma and Lung cancer
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7. Miscellaneous tumor markers
• Prostate Specific Antigen (PSA)
• Produced in the epithelial cells of the prostatic ducts
• Consists of two forms: free and complexed
• In healthy men, some amounts of PSA can be detected
• PSA is elevated in prostate infection, irritation and benign prostate
enlargement
• Methodology detects both forms
• Proteins- used to monitor therapy
• Examples
• Beta-2-Microglobulin
• Reflects cell turnover
• Immunoglobulins
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