Glypican-3 is a protein on the outer surface of cells that helps control signals that tell a cell whether to grow. The liver and other organs in a developing baby make large amounts before birth, and production almost stops afterward. Healthy liver tissue in a child or adult makes very little of it. Because normal adult tissue makes so little, glypican-3 is useful to pathologists. Tumors made of cells that behave like the developing liver switch it back on, and a stain can show that.
How is glypican-3 tested and reported?
Glypican-3 is detected using immunohistochemistry, a test that uses antibodies to find a specific protein in a tissue sample. Where the protein is present, the cells take up a colored stain that the pathologist can see under the microscope.
The result is reported as positive when staining is seen and negative when it is not. The report may describe the staining as membranous, meaning it outlines the edges of the cells, or cytoplasmic, meaning it fills the body of the cell. Both patterns count as positive. Reports sometimes abbreviate it as GPC3.
Which tumors are positive for glypican-3?
Glypican-3 is characteristically positive in tumors made of liver-type or yolk sac-type cells.
- Hepatoblastoma. The commonest liver cancer of childhood.
- Hepatocellular carcinoma. The commonest liver cancer in adults. Glypican-3 is particularly useful here, because it is usually negative in noncancerous liver conditions that can look similar under the microscope.
- Yolk sac tumor. A germ cell tumor of the testicle or ovary.
- Some other tumors. Including certain melanomas and squamous cell carcinomas, which is why the result is not interpreted on its own.
How is the result used?
Glypican-3 is rarely used alone. It is one member of a group of stains applied together when a pathologist needs to work out what a tumor is made of. The pattern across the group provides the answer.
In liver tumors, glypican-3 is usually run alongside stains such as HepPar-1 and arginase-1, which mark liver cells, and alpha-fetoprotein. In a liver biopsy, the question is often whether a nodule is a cancer or a noncancerous change. A positive glypican-3 result favors cancer, and a negative result does not exclude it. Roughly a quarter of hepatocellular carcinomas are negative, particularly well-differentiated ones, so the stain supports a diagnosis rather than settling it.
Does glypican-3 have anything to do with inherited conditions?
The gene that makes glypican-3, called GPC3, is on the X chromosome. Children born with a non-working copy have a condition called Simpson-Golabi-Behmel syndrome, an overgrowth condition that raises the risk of several childhood tumors, including hepatoblastoma and nephroblastoma.
That connection is about the gene being absent from birth, which is the opposite of what the stain detects in a tumor. A positive glypican-3 stain on a tumor says nothing about whether this syndrome is present, and it carries no implications for your family. If an overgrowth condition is suspected for other reasons, doctors assess it separately with a genetic test on normal tissue.
Questions to ask your doctor
- Was a glypican-3 stain performed on my tissue sample, and was it positive or negative?
- Which other stains were performed alongside it?
- What does the pattern across all the stains tell you about my diagnosis?
- If glypican-3 was negative, does that change the diagnosis or rule anything out?
- Was this stain used to tell a cancer apart from a noncancerous change in the liver?
- Does this result affect my treatment plan?
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