Tumor Marker:- Part 3 – Alk.phosphatase, CK, LDH, Acid phosphatase, and PSA

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

Sources of Alkaline phosphatase

The liver isoenzyme is more stable than the bone isoenzyme.
Placental isoenzyme is produced by the trophoblastic cells.
1. placental isoenzyme is also raised in pregnant women.
2. This was discovered by the Fishman in 1968.
3. This was the first tumor marker along with AFP and CEA.
Alkaline phosphatase marker is raised in:
1. Metastatic tumors of bone or liver.
2. Prostatic cancer with bone metastasis. There is osteoblastic activity and markedly raised the 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 (Source2)
1. Adult = 30 to 120 units/L
2. Old people = Higher than the adult’s value.
3. Children / adolescent:
  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 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 concentration in the heart muscles, skeletal muscles, and the brain.
Creatine kinase is a dimer consisting of two subunits (polypeptide chains):
1. CK – M
2. CK – B
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.

Isoenzyme of Creatine kinase

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

This is an enzyme in the action of the glycolytic pathway, and it is released when there is cell membrane damage.
LDH is found in the cells of Herat, RBCs, kidneys, liver, brain, lungs, and skeletal muscles.
1. When there is an injury to cells then LDH enters into the blood.
2. This not a good indicator of the cell injury because of its presence in most of the tissue.
Its level correlates with the tumor mass and gives a prognostic indicator of the progress of the disease.
LDH isoenzymes are:
1. LDH-1 is 17 to 27% and the main source is the heart.
2. LDH-2 is 27 to 37%. it is present in the reticuloendothelial system. This is the main component of LDH.
3. LDH-3 is 18 to 25% and is mainly present in the lung.
4. LDH-4 is 3 to 8%, is present in the kidney, pancreas, and placenta.
5. LDH-5 is 0 to 5%, is present in the skeletal muscles and liver.
Isoenzyme LD-5 is associated with liver metastasis.
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.
An elevated level of LDH in the urine indicates neoplasm or injury to the urogenital system.
LD – 5 positive in the spinal fluid indicates metastasis to the central nervous system.
Normal LDH level (Source 2):
1. Adult/elderly = 100 to 190 units/L at 37 °C

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 of prostatic cancer, the acid phosphatase decreases to normal in several days.
  1. When the patient is treated with estrogen therapy, then 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 the total acid phosphatase.
This is produced primarily by the prostate and raised in:
1. Prostatic cancer.
2. Osteogenic sarcoma.
3. Multiple myelomas.
4. metastasis to bone.

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

Prostatic specific antigen and types

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 of the treatment.
The sensitivity of PSA is 70% at the cut off value of 4.0 µg/L.
Specificity more than 90%, if cut off value, is raised to 8 µg/L.
The level of PSA correlates with the stage of the disease.
Measure PSA:
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.