MUC4: Definition

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MUC4 is a protein that belongs to a family of proteins called mucins. Mucins help form the protective layer of mucus that covers surfaces such as the airways and the digestive tract. Pathologists test for MUC4 mainly to help identify two rare sarcomas: low-grade fibromyxoid sarcoma and sclerosing epithelioid fibrosarcoma.

MUC4 is a test result, not a diagnosis. It is one of the stains a pathologist uses to determine which cell types are present. This article explains why pathologists test for MUC4 and what a positive or negative result means in your pathology report.

Where is MUC4 normally found?

In normal tissue, MUC4 is found mainly in epithelial cells that line surfaces and glands. These include the cells lining the airways, the stomach and intestines, and some glands. MUC4 is not usually found in the cells that make up normal fibrous tissue.

How do pathologists test for MUC4?

Pathologists test for MUC4 using immunohistochemistry (IHC). In this test, a thin slice of tissue on a glass slide is treated with an antibody that sticks to MUC4. A chemical reaction then colors any cell containing MUC4 brown, making it visible under the microscope. In positive tumors, the staining is usually strong and fills the cell.

Why do pathologists test for MUC4?

Pathologists use MUC4 to confirm what type of cells are present. It does not predict how a tumor will respond to a particular treatment. Pathologists test for MUC4 in the following situations:

To identify low-grade fibromyxoid sarcoma. This slow-growing soft-tissue cancer consists of bland spindle cells. It can look very similar to noncancerous fibrous tumors. Almost all low-grade fibromyxoid sarcomas are strongly MUC4-positive, while most look-alike noncancerous tumors are negative.
To identify sclerosing epithelioid fibrosarcoma. This rare sarcoma is closely related to low-grade fibromyxoid sarcoma. Most cases are positive for MUC4.
To identify glands in synovial sarcoma. Some synovial sarcomas contain small glands, which are often MUC4-positive.

Many carcinomas, cancers that start from epithelial cells, are also MUC4-positive. For this reason, MUC4 is most useful in soft tissue tumors, where it helps distinguish these sarcomas from other spindle cell tumors.

What does a positive MUC4 result mean?

A positive result means the tested cells contain MUC4. Your report may describe the result as “positive,” “reactive,” or say that MUC4 “is expressed.” In a soft tissue tumor made of bland spindle cells, strong and diffuse staining supports low-grade fibromyxoid sarcoma.

Low-grade fibromyxoid sarcoma can also be confirmed with a molecular test. Most cases have a fusion involving the FUS gene.

What does a negative MUC4 result mean?

A negative result means the tested cells do not contain MUC4. Your report may describe the result as “negative,” “nonreactive,” or “not expressed.” In a soft tissue spindle cell tumor, a negative result makes low-grade fibromyxoid sarcoma unlikely and supports another diagnosis.

Questions to ask your doctor

Why was MUC4 tested on my tumor?
Was the MUC4 result positive or negative?
What other stains were done along with MUC4?
Was molecular testing done to confirm the diagnosis?
What is the final diagnosis in my report?
Is the tumor noncancerous or cancerous?
Does the MUC4 result affect my treatment or follow-up?