Tumor Markers

• There are various specific tumor markers for various types of malignancies.
• Following is the list of tumor markers.
  1. Alkaline phosphatase.
  2. Creatinine Kinase.
  3. Lactate dehydrogenase.
  4. Prostatic acid phosphatase.
  5. Prostatic specific antigen.
  6. Adrenocorticotropic hormone.
  7. Calcitonin.
  8. HCG
  9. Carcinoembryonic antigen (CEA).
  10. AFP
  11. CA 15-3
  12. CA 19-9
  13. CA 50
  14. CA 72-4
  15. CA 125
  16. CA 549

Alkaline Phosphatase

1. Alkaline phosphatase is present in all the tissue, but the maximum amount is found in the liver, bone, and placenta.

2. The liver isoenzyme is more stable than the bone isoenzyme.
3. Placental isoenzyme is produced by the trophoblastic cells.
   1. Placental isoenzyme is also raised in pregnant women.
   2. This was discovered by Fishman in 1968.
   3. This was the first tumor marker, along with AFP and CEA.
4. The alkaline phosphatase  marker is raised in the following ways:
   1. Metastatic tumors of bone or liver.
   2. Prostatic cancer with bone metastasis. There is osteoblastic activity and a markedly raised level.
   3. Breast cancer metastasis to the bone with osteolytic activity and mildly raised level.
   4. Leukemia, Lymphoma, and sarcoma with metastases to the liver.
   5. This may be raised in other malignancies like ovarian, lung, trophoblastic, gestation tumors, seminoma, Hodgkin’s lymphoma, and GIT tumors.

Normal Alkaline phosphatase 

Source 2

1. Adult = 30 to 120 units/L
2. Old people = Higher than the adult’s value.
3. Children/adolescents:
   1. <2 years = 85 to 235 units/L.
   2. 2 to 8 years = 65 to 210 units/L.
   3. 9 to 15 years = 60 to 300 units/L.
   4. 16 to 21 years = 30 to 300 units/L.

Creatine Kinase (CK)

1. Creatine kinase is the enzyme that activates creatine in the muscles by transferring a high-energy phosphate group in the reaction. This reaction is reversible.
   1. Creatine + ATP ↔ Creatine phosphate + ADP
   2. CK is found in high concentrations in the heart muscles, skeletal muscles, and the brain.
2. Creatine kinase is a dimer consisting of two subunits (polypeptide chains):
   1. CK – M
   2. CK – B
3. There are three isoenzymes:
   1. CK-1 (BB). is present in the brain, prostate, GIT, bladder, lungs, uterus, and placenta.
   2. CK-2 (MB) is present in high concentrations in the cardiac muscles.
   3. CK-3 (MM) is present in the cardiac and skeletal muscles.

3. This is raised in:
   1. Prostatic cancer.
   2. Small cell carcinoma of the lung.
   3. Maybe elevated in breast, ovary, stomach, and colon cancers.

Normal Total CPK (Source 2):

1. Adult/elderly
   1. Male = 55 to 170 units/L
   2. Female = 30 to 135 units/L
      1. Values are higher after the exercise.
   3. Newborn = 68 to 580 units/L

Lactate Dehydrogenase (LDH)

1. This is an enzyme in the action of the glycolytic pathway, and it is released when there is cell membrane damage.

2. LDH is found in the cells of Herat, RBCs, kidneys, liver, brain, lungs, and skeletal muscles.
3. When there is an injury to cells then, LDH enters the blood.
4. This is not a good indicator of cell injury because of its presence in most of the tissue.
5. Its level correlates with the tumor mass and gives a prognostic indicator of the progress of the disease.

LDH isoenzymes are:

1. Isoenzyme LD-5 is associated with liver metastasis.
2. LDH is a nonspecific tumor marker and is raised in:
   1. Liver cell carcinoma.
   2. Lymphomas.
   3. Acute leukemias.
   4. Germ cell testicular tumors.
   5. Breast cancer.
   6. Colon cancer.
   7. Stomach cancer.
   8. Lung cancer.
3. An elevated level of LDH in the urine indicates neoplasm or injury to the urogenital system.
4. LD-5 positive in the spinal fluid indicates metastasis to the central nervous system.

Normal LDH level (Source 2):

1. 1. Adult/elderly = 100 to 190 units/L at 37 °C

Neuron-specific Enolase (NSE)

1. Neuron-specific enolase (NSE) is the isoenzyme in the glycolytic pathway identified by the immunoassay and found mostly in neuron and neuroendocrine cells.
2. This is a glycolytic pathway.
3. Indication:
   1. It monitors treatment and predicts relapse in small-cell lung cancer.
4. Raised level of NSE:
5. It is raised neuroendocrine tumors:
   1. Small cell carcinoma of the lung.
      1.  It is found in 68% of limited diseases.
      2. 87% is found in the extensive disease.
6. Use for monitoring the following:
   1. Neuroblastoma.
   2. Pheochromocytoma.
   3. Carcinoid.
   4. Medullary carcinoma of the thyroid.
   5. Melanoma.
   6. Pancreatic endocrine tumors.

Prostatic acid phosphatase

1. Acid phosphatase is found in many tissues, including the liver, blood vessels, red blood cells, platelets, and bone marrow.
   1. The maximum concentration is found in the prostate gland.
   2. The estimation of acid phosphatase is advised for:
      1. The diagnosis of prostatic carcinoma.
      2. Staging of the prostatic carcinoma.
      3. To monitor the efficacy of the treatment of prostatic carcinoma.
   3. The level is raised when the prostatic carcinoma has metastasized beyond the capsules to the other parts of the body, especially to the bone.
   4. In the case of complete curative surgery for prostatic cancer, the acid phosphatase decreases to normal in several days.
      1. When the patient is treated with estrogen therapy, it returns to normal in several weeks.
   5. Prostatic acid phosphatase (PAP) is a better indicator and most clinically significant.
      1. PAP is more accurate than total acid phosphatase.
2. This is produced primarily by the prostate and raised in:
   1. Prostatic cancer.
   2. Osteogenic sarcoma.
   3. Multiple myelomas.
   4. Metastasis to the bone.

Prostatic specific antigen (PSA)

1. PSA is a glycoprotein normally found in the cytoplasm of the prostatic epithelial cells.
2. This antigen is detected in all males, but its level is markedly increased in prostatic carcinoma.
3. Its level is related to the size of the tumor.

1. The use of PSA:
   1. This is specific for the diagnosis of prostatic cancer.
   2. It is used to detect, stage, and monitor the treatment of prostatic carcinoma.
   3. Its use is more specific for monitoring the treatment.
2. The sensitivity of PSA is 70% at the cut-off value of 4.0 µg/L.
3. Specificity is more than 90% if the cut-off value is raised to 8 µg/L.
4. The level of PSA correlates with the stage of the disease.
5. Measure PSA for the follow-up of prostatic carcinoma:
   1. Every 3 months after the surgery during the first year.
   2. After 4 months in the second year.
   3. After 6 months every year.

Questions and answers: