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Tumor Markers:- Part 8 – Alpha-fetoprotein (AFP)

January 8, 2025Lab TestsTumor marker

Table of Contents

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  • Alpha-fetoprotein (AFP)
        • What sample is needed for Alpha-Fetoprotein (AFP)?
        • What are the Indications for Alpha-Fetoprotein (AFP)?
        • How will you define Alpha-Fetoprotein (AFP)?
        • What is the structure of Alpha-fetoprotein (AFP)?
        • What are the functions of the Alpha-fetoprotein (AFP)?
      • Maternal serum AFP is raised or higher in the neural tube defect:
        • What is the normal Alpha-Fetoprotein (AFP)?
      • What is the role of Alpha-fetoprotein (AFP) as a tumor marker?
        • What are the values in Liver cell carcinoma?
        • What is the role of AFP as a tumor marker for the Germ cell tumor (nonseminomatous tumor)?
        • What are the causes of increased AFP (Maternal AFP)?
        • What are the causes of decreased AFP?
      • Questions and answers:

Alpha-fetoprotein (AFP)

What sample is needed for Alpha-Fetoprotein (AFP)?

  1. The patient’s serum is required.
  2. Can take a random sample, and no fasting is needed.

What are the Indications for Alpha-Fetoprotein (AFP)?

  1. For the diagnosis of liver cell carcinoma.
  2. Patients with chronic active hepatitis.
  3. Patients with cirrhosis and positive serology (HBV and HCV) should be tested with AFP and ultrasound abdomen.
  4. AFP is a tumor marker for yolk sac tumors.
  5. AFP raised in hepatoid gastric carcinoma.

How will you define Alpha-Fetoprotein (AFP)?

  1. In 1960, the discovery of oncofetal antigens AFP and CEA started the development of tumor markers.
    1. Alpha-fetoprotein (AFP) was found in the serum of mice with liver cell carcinoma and later in the sera of humans with liver cell carcinoma.
    2. Alpha-fetoprotein (AFP) is a tumor marker for liver and germ cell (non-seminoma) carcinoma.
  2. This is a glycoprotein. This consists of a single polypeptide chain and has a 4% carbohydrate.
    1. The yolk sac produces this in small amounts, and the liver produces an abundant amount in the fetus.
  3. AFP is produced by:
    1. Yolk sac.
    2. Then, by the fetal liver.
    3. It peaks at 10 to 13 weeks of gestation, then declines to <100 µg/L by term. By the age of 2 years, reaches adult levels <5 µg/L.
  4. It is normal after about 18 months of birth.
Alpha-Fetoprotein (AFP): AFP in fetus

Alpha-Fetoprotein (AFP): AFP in fetus

Alpha-Fetoprotein (AFP): AFP in the fetus

Alpha-Fetoprotein (AFP): AFP in the fetus

  1. It is close to albumin, genetically and structurally.
    1. The gene coding for both is chromosome 4q.
  2. Its concentration is 10% of that of albumin.

What is the structure of Alpha-fetoprotein (AFP)?

  1. The fetal liver produces an alpha-1 globulin called alpha-fetoprotein. It becomes the dominant fetal serum protein in the first trimester.
    1. It reaches a peak at 12 weeks, then declines to 1% of the peak at birth.
    2. By the age of 1 year, there is a marked decrease.
  2. Alpha-fetoprotein (AFP) is a glycoprotein with a molecular weight of 70 kDa.
  3. It has a single polypeptide chain and around 5% of carbohydrates.
  4. Alpha-fetoprotein (AFP) is synthesized in large quantities by the fetal yolk sac and liver during embryonic development.
  5. It is the major protein in fetal circulation.
  6. Alpha-fetoprotein (AFP) is genetically and structurally identical to albumin.

What are the functions of the Alpha-fetoprotein (AFP)?

  1. AFP has increased in pregnancy, usually not >100 ng/mL.
  2. Its main role is to bind and transport substances that are not water-soluble, such as steroid hormones, lipids, vitamins, and bilirubin.
  3. Maternal serum AFP is lower than expected in Down’s syndrome.
    1. AFP detects ≤25% of the cases.
    2. Ultrasound is used to calculate the gestational stage, which is important to calculate the risk of Down’s syndrome.
    3. AFP is 25% to 30% lower in Down’s syndrome.
    4. Down syndrome = Trisomy 21 and Mongolism. It is the most common autosomal trisomy.
Down's syndrome

Down’s syndrome

Maternal serum AFP is raised or higher in the neural tube defect:

  1. A level> 1000 µg/L indicate malignancy:
    1. At this level, 50% of liver cell carcinomas are diagnosed.
    2. It is ideal for diagnosing a liver tumor below the size of 5 cm.
    3. To find these small tumors, the cut-off value has to be set at a lower level between 200 to 1000 µg/L.
  2. In healthy individuals, it is 10 µg/L.

What is the normal Alpha-Fetoprotein (AFP)?

  1. Adult = <40 ng/mL  (<40 µg/L)
  2. Child <1 year = <30 ng/mL
  3. Mid-trimester = 10 to 15 ng/mL.

Another source

  • 0 to 15 ng/mL

What is the role of Alpha-fetoprotein (AFP) as a tumor marker?

What are the values in Liver cell carcinoma?

  1. AFP is raised in 80% of liver cell carcinoma.
  2. >500 ng/mL is diagnostic of liver cell carcinoma.
  3. AFP may be raised for 18 months before the S/S appears.
  4. AFP is a sensitive indicator of recurrence.
  5. AFP >1000 ng/mL in 50% of the cases indicates tumor size >3 cm in diameter.
AFP in Liver cell carcinoma (Hepatoma)

AFP in Liver cell carcinoma (Hepatoma)

  1. In 90% of the cases, AFP >200 ng/mL, and 70% have a concentration of AFP >400 ng/mL.
    1. In 90% of cases of liver cell carcinoma, Alpha-Fetoprotein (AFP) is raised >200 ng/mL.
    2. In 70% of the cases, liver cell carcinoma Alpha-Fetoprotein (AFP) is raised >400 ng/mL.
    3. In benign liver diseases, alpha-fetoprotein (AFP) rarely is >400 ng/mL.
  2. This is more likely raised in immature carcinoma than the mature type of carcinoma.
  3. An initial high level indicates a poor prognosis.
  4. Failure to come to normal indicates a problem with surgery where there is incomplete resection or metastasis.
  5. The postoperative decrease followed by an increase in the AFP indicates recurrence.
  6. If there is a short doubling in the AFP value, suggest metastasis at the time of surgery.
  7. AFP is useful for liver cell carcinoma:
    1. Diagnosing.
    2. Prognosis.
    3. Monitor therapy.

What is the role of AFP as a tumor marker for the Germ cell tumor (nonseminomatous tumor)?

  1. Yolk sac tumors lead to an increase in  AFP, which correlates with the tumor prognosis; e.g., >1000 ng/mL is associated with a poor prognosis.
  2. Alpha-fetoprotein (AFP) is raised in Embryonic cell carcinoma in 27% of the cases.
  3. Alpha-fetoprotein (AFP) is raised in Malignant teratoma in 60% of the cases.
  4. Alpha-fetoprotein (AFP) is increased in Testicular teratocarcinoma in 75% of the cases.
  5. Choriocarcinoma element is seen in seminoma, yolk sac, teratoma, and embryonal cell carcinoma.
  6. Pancreatic carcinoma AFP is positive in 23% of the cases.
  7. Gastric carcinoma is AFP 18% positive.
  8. Bronchogenic carcinoma is 7% positive.
  9. Colon carcinoma is 5% positive.

What are the causes of increased AFP (Maternal AFP)?

  1. Multiple pregnancy.
  2. Race (10% to 15%), higher level in blacks.
  3. Open neural tube defects like:
    1. Open spina bifida.
    2. Encephalocele.
    3. Anencephaly.
    4. Myelocele.
  4. Hydrops fetalis.
  5. Intrauterine death.
  6. Feto-metrnal haemorrage.
  7. Cystic hygroma.
  8. Renal disorders like polycystic kidneys, renal agenesis, and urethral obstruction.
  9. Sacrococcygeal sarcoma.
  10. Tetralogy of Fallot.
  11. Turner syndrome.
  12. Oligohydramnios.
  13. Placental infarction, thrombosis, inflammation, very large placenta, and cystic changes.
  14. Cystic hygroma.
  15. Oloigohydroamnios.

What are the causes of decreased AFP?

  1. Down’s syndrome.
  2. Long-standing death of the fetus.
  3. Hydatidiform mole.
  4. Choriocarcinoma.
  5. Increased maternal weight.
  6. Females with diabetes mellitus.
  7. Pseudopregnancy and no pregnancy.

 

Questions and answers:

Question 1: What is the level of Alpha-Fetoprotein (AFP) for the diagnosis of liver cell carcinoma?
Show answer
Alpha-Fetoprotein (AFP) >500 ng/mL is diagnostic of liver cell carcinoma.
Question 2: What is the relation of Alpha-Fetoprotein (AFP) to albumin?
Show answer
Alpha-Fetoprotein (AFP) is genetically and structurally similar to albumin.
  • Note: In some books on the same page, the values are given in ng/mL and ng/dL. It is difficult for me to decide which one I can follow.
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