CD31: Definition

Print this article

CD31 is a protein found on the surface of endothelial cells, the cells that line the inside of blood vessels. Pathologists test for CD31 to find out whether the cells in a tissue sample are endothelial cells. This helps identify tumors that start from blood vessels, called vascular tumors. CD31 is also known as PECAM-1, which stands for platelet endothelial cell adhesion molecule 1.

CD31 is a test result, not a diagnosis. It is one of the stains a pathologist uses to determine what types of cells are present. This article explains why pathologists test for CD31 and what a positive or negative result means in your pathology report.

Where is CD31 normally found?

Endothelial cells make CD31. It is strongly present in the cells lining small and large blood vessels, and it is usually weaker in the lining of lymphatic vessels. In endothelial cells, CD31 helps neighboring cells hold together and helps white blood cells pass through the vessel wall into tissue.

Some other normal cells also make CD31. These include platelets, the cells in the bone marrow that make platelets, and several types of white blood cells. These include macrophages, immune cells that clean up damaged tissue. Pathologists take these cells into account when interpreting the result.

How do pathologists test for CD31?

Pathologists test for CD31 using immunohistochemistry (IHC). In this test, a thin slice of tissue on a glass slide is treated with an antibody that sticks to CD31. A chemical reaction then colors any cell containing CD31 brown, making it visible under the microscope. In endothelial cells, the brown color usually outlines each cell’s edge.

Normal blood vessels in almost every tissue sample also stain for CD31. These vessels act as a built-in check that the test worked properly.

Why do pathologists test for CD31?

Pathologists use CD31 to confirm what cell types are present. It does not predict how a tumor will respond to a particular treatment. Pathologists test for CD31 in the following situations:

To confirm a vascular tumor. Tumors made of endothelial cells are usually CD31-positive. Examples include hemangioma, pyogenic granuloma, Kaposi sarcoma, epithelioid hemangioendothelioma, and angiosarcoma.
To identify a tumor that does not look vascular. Some endothelial-cell cancers do not form obvious blood vessels under the microscope. They can look like other types of cancer, such as a carcinoma or melanoma. A positive CD31 result helps show that the tumor started from blood vessel cells.
To look for tumor cells inside blood vessels. CD31 highlights the lining of blood vessels. This helps the pathologist confirm lymphovascular invasion, which means cancer cells have entered a vessel.

CD31 shows that cells are endothelial cells, but it does not show whether a tumor is noncancerous or cancerous. Both a hemangioma and an angiosarcoma are positive for CD31. The pathologist makes that distinction by looking at the tumor under the microscope and considering other test results.

What does a positive CD31 result mean?

A positive result means the tested cells contain CD31. Your report may describe the result as “positive,” “reactive,” or say that CD31 “highlights” or “is expressed by” the tumor cells.

When the tumor cells are positive, the result supports a tumor made of endothelial cells. The pathologist confirms that the stained cells are the tumor cells, and not normal blood vessels or macrophages mixed in with the tumor. When CD31 is used to look for lymphovascular invasion, a positive result shows a vessel lining surrounding a group of tumor cells.

What does a negative CD31 result mean?

A negative result means the tumor cells do not contain CD31. Your report may describe the result as “negative,” “nonreactive,” or “not expressed.” In most cases, a negative result makes a vascular tumor unlikely. Normal blood vessels in the same sample are usually still positive, which confirms that the test worked.

A negative result does not always rule out a vascular tumor. A small number of vascular tumors show only weak or focal CD31 staining. For this reason, pathologists usually test CD31 with other markers.

What other markers are tested with CD31?

Pathologists rarely rely on a single stain. CD31 is usually part of a group of tests, called a panel, chosen to answer a specific question. Markers commonly tested with CD31 include:

ERG. Another marker of endothelial cells. It stains the cell nucleus, which can make it easier to interpret than CD31.
CD34. Present in most blood vessel tumors, but also in several other types of tumors. It is less specific for endothelial cells than CD31.
FLI1. A nuclear marker present in endothelial cells and some other tumors.
D2-40. A marker of the cells lining lymphatic vessels. It helps separate lymphatic vessels from blood vessels.
HHV-8. A stain for the virus that causes Kaposi sarcoma. It helps confirm that diagnosis.

Not every sample needs every marker. The pathologist chooses the panel based on what is seen under the microscope and the diagnoses being considered.

Questions to ask your doctor

Why was CD31 tested on my sample?
Were the tumor cells positive or negative for CD31?
Does the CD31 result confirm that my tumor started from blood vessel cells?
Is the tumor noncancerous or cancerous, and how was that decided?
What other markers were tested along with CD31?
Did CD31 show any cancer cells inside blood vessels?
Does the CD31 result affect my treatment?
Are any other tests needed to confirm the diagnosis?