Introduction
- Alpha-Fetoprotein (AFP) is a glycoprotein mainly produced by the fetal liver, yolk sac, and gastrointestinal tract during fetal development.
- AFP is an important tumor marker used in the diagnosis and monitoring of certain cancers.
- It is commonly measured in patients with hepatocellular carcinoma (HCC) and germ cell tumors.
- Maternal serum AFP is also used for prenatal screening to detect fetal abnormalities.
- AFP testing helps in the diagnosis, prognosis, and monitoring of disease progression and treatment response.
- The test is simple, reliable, and widely performed in clinical laboratories.
- AFP levels vary with age, pregnancy, and certain disease conditions.
Definition of Alpha-Fetoprotein
Alpha-Fetoprotein (AFP) is a fetal plasma glycoprotein produced mainly by the fetal liver, yolk sac, and gastrointestinal tract. In adults, AFP is present in very low concentrations, but its levels increase in certain liver diseases, germ cell tumors, and during pregnancy, making it a valuable tumor marker and prenatal screening marker.
Structure and Characteristics
Structure
- AFP is a single-chain glycoprotein.
- It has a molecular weight of approximately 70 kDa.
- It is structurally similar to serum albumin.
- AFP belongs to the albumin gene family.
Characteristics
- Synthesized mainly by the fetal liver.
- Present at high concentrations in fetal blood.
- Levels decrease rapidly after birth.
- Present in very low concentrations in healthy adults.
- Used as a tumor marker and prenatal screening marker.
- Measured in serum or plasma using immunoassays.
Normal Reference Range
| Patient Group | Reference Range |
|---|---|
| Healthy Adults | < 10 ng/mL |
| Pregnant Women | Varies with gestational age |
| Newborns | Very high at birth and gradually decreases during infancy |
Synthesis
Alpha-Fetoprotein (AFP) is synthesized mainly by:
- Fetal liver (major site)
- Yolk sac (during early fetal development)
- Fetal gastrointestinal tract
After birth, AFP production decreases rapidly, and only very low levels are present in healthy adults.
Regulation
- AFP production is highest during fetal life.
- Levels gradually decrease after birth.
- AFP levels increase in pregnancy, hepatocellular carcinoma (HCC), germ cell tumors, and some liver diseases.
Functions of Alpha-Fetoprotein
- Transports fatty acids, bilirubin, and hormones during fetal life.
- Maintains osmotic pressure in the fetus (similar to albumin).
- Supports normal fetal growth and development.
- May help regulate the fetal immune system.
- Acts as an important tumor marker in adults.
Specimen Requirements
- Specimen: Serum or plasma
- Sample Volume: 2–5 mL venous blood
- Collection Tube: Plain tube or serum separator tube (SST)
- Storage: Store at 2–8°C if analyzed within 48 hours; freeze for longer storage.
- Avoid hemolyzed or contaminated samples.
Methods for AFP Estimation
The following laboratory methods are commonly used:
- Enzyme-Linked Immunosorbent Assay (ELISA)
- Chemiluminescent Immunoassay (CLIA)
- Electrochemiluminescence Immunoassay (ECLIA)
- Radioimmunoassay (RIA)
- Immunoturbidimetric Assay (less commonly used)
Principle of AFP Test
- The Alpha-Fetoprotein (AFP) test is based on the antigen–antibody reaction.
- AFP present in the patient’s serum binds specifically to anti-AFP antibodies.
- The antigen–antibody complex produces a measurable signal, which is directly proportional to the AFP concentration.
Procedure for AFP Testing
- Collect 2–5 mL of venous blood.
- Separate the serum by centrifugation.
- Add the serum sample to the test system containing anti-AFP antibodies.
- Incubate according to the manufacturer’s instructions.
- Add the detection reagent and wash if required.
- Measure the signal using the analyzer.
- Compare the result with the calibration curve and report the AFP concentration.
Interpretation of AFP Results
| AFP Level | Interpretation |
|---|---|
| < 10 ng/mL | Normal in healthy adults |
| 10–500 ng/mL | May be seen in chronic liver disease, hepatitis, cirrhosis, or pregnancy |
| > 500 ng/mL | Strongly suggests hepatocellular carcinoma (HCC) or non-seminomatous germ cell tumors (to be interpreted with clinical findings and imaging) |
Causes of Increased AFP Levels
Elevated AFP levels may be seen in the following conditions:
- Hepatocellular carcinoma (HCC)
- Non-seminomatous germ cell tumors (testicular or ovarian)
- Chronic hepatitis
- Liver cirrhosis
- Pregnancy (normal physiological increase)
- Neural tube defects in the fetus
- Multiple pregnancy
- Liver regeneration after injury
Causes of Decreased AFP Levels
Low AFP levels may occur in:
- Healthy adults (normal finding)
- Down syndrome (Trisomy 21) during pregnancy
- Edwards syndrome (Trisomy 18) during pregnancy
- Incorrect estimation of gestational age
- Fetal death or miscarriage
Clinical Applications of AFP
AFP testing is widely used in clinical practice for:
- Screening and monitoring hepatocellular carcinoma (HCC)
- Diagnosis and follow-up of germ cell tumors
- Monitoring response to cancer treatment
- Detection of tumor recurrence after treatment
- Prenatal screening for neural tube defects and certain chromosomal abnormalities
- Assessment of chronic liver diseases, such as hepatitis and cirrhosis
- Monitoring disease progression in patients with liver disorders