Alpha-fetoprotein (AFP): Definition

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Alpha-fetoprotein, usually shortened to AFP, is a protein made in large amounts by the liver and the yolk sac of a developing baby before birth. After birth, the amount falls steadily, and by around 8 months of age it reaches the low level found in healthy older children and adults.

AFP appears in pathology and laboratory reports in two different ways. It is most often a blood test, where the amount circulating in the blood is measured. It can also be used as a stain applied to tissue, where it helps show what a group of cells is made of. Both uses are explained below.

Why is alpha-fetoprotein measured?

Some tumors are made of cells that behave like the developing liver or yolk sac, and those cells keep making alpha-fetoprotein. When a tumor of this kind is present, AFP leaks into the blood and the level rises, sometimes to many thousands of times the normal amount.

That makes AFP useful in three ways. It supports the diagnosis when a mass is found. It shows whether treatment is working, because the level falls as the tumor shrinks. It also detects recurrence, because a rising level after treatment can appear weeks or months before anything is visible on a scan.

Which tumors raise alpha-fetoprotein?

Alpha-fetoprotein is raised in tumors made of cells resembling the developing liver or yolk sac. The commonest are listed below.

Hepatoblastoma. The commonest liver cancer of childhood. AFP is raised in roughly 9 out of 10 children with this diagnosis.
Hepatocellular carcinoma. The commonest liver cancer in adults. AFP is raised in some but not all cases, so a normal level does not exclude it.
Yolk sac tumor. A germ cell tumor of the testicle or ovary. AFP is characteristically high.
Mixed germ cell tumors. Raised when a yolk sac component is present.

A raised AFP does not always mean cancer. The level also rises in pregnancy, in hepatitis and other causes of liver inflammation, in cirrhosis, and while the liver is regenerating after injury. This is why an AFP result is interpreted alongside imaging, the physical examination, and, where a mass is present, the pathology report.

Why does age matter so much?

A healthy newborn has a very high alpha-fetoprotein level, and it falls over the first months of life. A number that would be markedly abnormal in a 3-year-old can be entirely normal in a 2-month-old.

For this reason, laboratories compare an AFP result in an infant against a range for the child’s age rather than the adult range. If your child’s report shows a high AFP and your child is very young, ask whether the number was compared against the range for their age. Make that comparison before drawing any conclusions.

What does a low alpha-fetoprotein mean in a liver tumor?

In most situations, a low result is reassuring. In a child with a liver tumor,r it is not. A hepatoblastoma with an AFP below 100 nanograms per milliliter at diagnosis is uncommon and has long been recognized as carrying a less favorable outlook.

Part of the reason has become clearer with better testing. Many tumors in this group turn out not to be hepatoblastoma at all, but a different childhood liver tumor called a rhabdoid tumor. An additional stain identifies it, and it is treated differently. A low AFP in this setting therefore prompts more testing rather than reassurance.

How is alpha-fetoprotein used as a stain on tissue?

In addition to being measured in blood, alpha-fetoprotein can be detected directly in a tissue sample using immunohistochemistry. This test uses antibodies that attach to the AFP protein inside cells. Where the protein is present, the cells take up a colored stain that the pathologist can see under the microscope.

A result is reported as positive when staining is seen and negative when it is not. A positive AFP stain supports a tumor made of liver-type or yolk sac-type cells. It is rarely used on its own and is usually part of a group of stains that together identify the cells.

How are the results reported?

A blood AFP result is reported as a number with units, most often nanograms per milliliter, alongside the laboratory’s reference range. Results measured over time are more informative than any single value, so your team will look at the trend.

A tissue AFP result appears in the pathology report among the other stains performed, usually as a simple positive or negative.

Questions to ask your doctor

What was my alpha-fetoprotein level, and what is the normal range for my age?
If this test was done on a young child, was the result compared against a range for their age?
Could something other than a tumor explain a raised level in my case?
Will AFP be used to follow my response to treatment, and how often will it be measured?
What level would you expect to see if treatment is working?
How long will AFP be monitored after treatment finishes?
What would a rising level mean, and what would happen next?
Was an AFP stain performed on my tissue sample, and what did it show?