Brachyury: Definition

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Brachyury is a protein that helps control how the body develops before birth. It is made by the notochord, a rod of cells in the early embryo that guides the formation of the spine. Pathologists test for brachyury to help diagnose chordoma, a rare cancer that develops from leftover notochord cells. The gene that makes brachyury is called TBXT.

Brachyury is a test result, not a diagnosis. It is one of the stains a pathologist uses to work out what type of tumor is present. This article explains why pathologists test for brachyury and what a positive or negative result means in your pathology report.

Where is brachyury normally found?

Brachyury is a type of protein called a transcription factor. It works inside the cell nucleus, switching other genes on and off. Before birth, cells in the notochord make it in large amounts.

As the baby develops, the notochord disappears, and its remains form part of the discs between the bones of the spine. After birth, almost no normal adult tissues contain brachyury. This makes it a very specific marker. Finding brachyury in a tumor strongly suggests the tumor came from notochord cells.

How do pathologists test for brachyury?

Pathologists test for brachyury using immunohistochemistry (IHC). In this test, a thin slice of tissue on a glass slide is treated with an antibody that sticks to brachyury. A chemical reaction then colors the nucleus of any cell containing brachyury brown so that it can be seen under the microscope.

Why do pathologists test for brachyury?

Pathologists use brachyury to confirm what cell types are present. It does not predict how a tumor will respond to a particular treatment. Pathologists test for brachyury in the following situations:

To confirm a chordoma. Chordomas usually develop in the bones at the base of the skull, in the spine, or in the sacrum, the bone at the bottom of the spine. Almost all chordomas are positive for brachyury.
To separate chordoma from chondrosarcoma. At the base of the skull, a chordoma and a chondrosarcoma can look very similar under the microscope and on imaging. Chordoma is positive for brachyury, while chondrosarcoma is negative. This difference matters because clinicians treat and follow the two tumors differently.
To separate chordoma from other tumors. Other tumors that can look like chordoma include metastatic carcinoma and myoepithelial tumors. These are usually negative for brachyury.
To identify a noncancerous notochord tumor. A benign notochordal cell tumor is a small, noncancerous growth of notochord cells inside a vertebra. It is also positive for brachyury. Pathologists and radiologists distinguish it from chordoma based on its appearance under the microscope and on imaging.

Brachyury is usually tested together with other markers. Chordomas are also positive for cytokeratins and often for S100. Combining these results makes the diagnosis more certain.

What does a positive brachyury result mean?

A positive result means the tumor cells contain brachyury. Your report may describe the result as “positive,” “reactive,” or say that brachyury shows “nuclear staining.” In a tumor of the skull base, spine, or sacrum, a positive result strongly supports a diagnosis of chordoma.

Some uncommon chordoma types show additional changes. A poorly differentiated chordoma is positive for brachyury but has lost a protein called INI1 (SMARCB1). A dedifferentiated chordoma contains areas that look like a different, high-grade cancer, and these areas are often negative for brachyury.

What does a negative brachyury result mean?

A negative result means the tumor cells do not contain brachyury. Your report may describe the result as “negative,” “nonreactive,” or “not expressed.” A negative result makes chordoma very unlikely and supports another diagnosis, such as chondrosarcoma.

Can brachyury changes be inherited?

Almost all chordomas are not inherited. In a very small number of families, several relatives develop chordoma. Some of these families carry an extra copy of the TBXT gene that is passed from parent to child. If more than one person in your family has had chordoma, your doctor may suggest genetic counseling.

Questions to ask your doctor

Why was brachyury tested on my tumor?
Was the brachyury result positive or negative?
Does the result confirm a chordoma?
Was chondrosarcoma ruled out?
What other stains were done along with brachyury?
Is my chordoma a conventional, poorly differentiated, or dedifferentiated type?
Should my family members be offered genetic counseling?