AE1/AE3


AE1/AE3 is a special laboratory test that detects proteins called cytokeratins, which are found in epithelial cells. Epithelial cells form the lining of many surfaces in the body, such as the skin, glands, and the inside of organs like the lungs, bladder, and digestive tract. AE1/AE3 is not a single protein but a mixture of two antibodies—AE1 and AE3—that together recognize a wide range of cytokeratins. Because most cancers that arise from epithelial cells (called carcinomas) produce cytokeratins, AE1/AE3 is a helpful tool for pathologists when diagnosing these tumours.

What types of normal cells and tissues express AE1/AE3?

AE1/AE3 staining highlights epithelial cells throughout the body. These include:

  • Squamous cells on the surface of the skin and lining the surface of the mouth, throat, large airways, and cervix.

  • Cells lining the respiratory tract, gastrointestinal tract, and urinary tract.

  • Glandular cells in organs like the breast, prostate, and salivary glands.

  • Trophoblasts, which are cells of the placenta during pregnancy.

In normal tissue samples, AE1/AE3 appears as a cytoplasmic stain (colour change in the body of the cell) with occasional accentuation along the edges of the cells. Liver tissue is often used as a built-in control during testing because its normal epithelial cells stain reliably with AE1/AE3.

How do pathologists test for AE1/AE3?

Pathologists use a technique called immunohistochemistry (IHC) to test for AE1/AE3. During this test, antibodies that bind to cytokeratins are applied to a tissue sample. If cytokeratins are present, a visible stain appears in the cytoplasm of the cells under the microscope. A positive result means that the cells contain cytokeratins, suggesting they are of epithelial origin. A negative result suggests the cells likely come from non-epithelial tissue, such as muscle, nerve, or blood-forming tissues.

AE1/AE3 is most often used as part of a panel of tests to help identify tumours when the origin is unclear, especially when only a few tumour cells are present or when inflammation or tissue damage makes diagnosis difficult.

What types of tumours express AE1/AE3?

AE1/AE3 is commonly positive in most carcinomas, which are cancers that arise from epithelial cells. Examples include:

AE1/AE3 is also helpful for identifying small amounts of metastatic carcinoma (cancer that has spread from another site) in lymph nodes, bone marrow, or surgical scars. In these cases, it can highlight isolated tumour cells that may be missed on routine stains.

However, not all cancers express AE1/AE3. Tumours that arise from non-epithelial cells—such as sarcomas, melanomas, lymphomas, and many brain tumours—are typically AE1/AE3 negative.

Why is AE1/AE3 important in a pathology report?

AE1/AE3 is important because it helps pathologists determine whether tumour cells come from epithelial tissue. This is especially useful when:

  • The tumour has an unclear origin.

  • There is very little tissue available for diagnosis.

  • The tissue is distorted by scarring, inflammation, or prior treatment.

  • Pathologists need to detect micrometastases (very small cancer deposits) in lymph nodes or other tissues.

AE1/AE3 may also help pathologists assess the depth of tumour invasion or identify areas of tumour budding—small clusters of tumour cells that break off from the main tumour and may be linked to a worse prognosis.

Because AE1/AE3 stains a wide range of epithelial tissues, it is not used on its own to make a diagnosis. Instead, it is part of a panel of tests used alongside other markers to give a more complete picture of the tumour.

Questions to ask your doctor

  • What does the AE1/AE3 result mean in my pathology report?

  • Does this result help determine where the cancer started?

  • Were other markers tested along with AE1/AE3?

  • Is this tumour of epithelial origin?

  • Does the AE1/AE3 staining help confirm that the tumour has spread or invaded nearby tissues?

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