E-cadherin

E-cadherin (also called cadherin-1) is a protein found on the surface of most epithelial cells. Epithelial cells are the cells that line many surfaces in the body, including the skin, glands, and the inside of organs such as the breast, stomach, and colon. E-cadherin helps these cells stick together and maintain their structure and organization. When E-cadherin is lost or not functioning properly, cells can become loose and are more likely to spread, a phenomenon often observed in certain types of cancer.

What does E-cadherin do?

E-cadherin plays a key role in cell adhesion, which means it helps cells stick to one another to form strong, stable tissues. It also helps maintain cell polarity, which refers to the proper arrangement of different parts of the cell. E-cadherin is attached to other proteins inside the cell that anchor it to the cell’s internal framework (cytoskeleton), allowing it to help control cell shape, growth, and movement.

What types of cells normally express E-cadherin?

E-cadherin is found in the cell membrane of most normal epithelial cells. This includes cells in the breast, colon, lung, skin, and many glands. The protein forms a strong, continuous ring around each cell, helping the cells stay attached. Some blood-forming cells, such as immature red blood cells, also express E-cadherin.

How do pathologists test for E-cadherin?

Pathologists use a test called immunohistochemistry (IHC) to look for E-cadherin in a tissue sample. In this test, a special antibody is used to detect E-cadherin, and the result is viewed under a microscope. If E-cadherin is present and working normally, it will appear as strong, continuous staining around the edges of the cells (called membranous staining). If E-cadherin is lost, the staining will be weak, patchy, or completely absent.

The result is reported as positive if normal staining is seen and negative if staining is lost or reduced. Sometimes E-cadherin expression is abnormal, such as when it is found in the nucleus or cytoplasm instead of the membrane, which can be a sign of a non-functional form of the protein.

What types of tumors show changes in E-cadherin?

Pathologists use E-cadherin to help diagnose and classify several types of tumors. In some cancers, E-cadherin is lost, and this change can affect how the tumor behaves.

• Breast cancer – E-cadherin is usually positive in ductal carcinoma, a common type of breast cancer. In contrast, it is typically lost in lobular carcinoma, which grows in a different pattern. This difference helps pathologists distinguish between these types.

• Stomach (gastric) cancer – Loss of E-cadherin is common in diffuse type gastric cancer, which tends to grow in a scattered, less cohesive pattern.

• Urothelial carcinoma – A rare aggressive form called plasmacytoid urothelial carcinoma often shows loss of E-cadherin, which contributes to the discohesive appearance of the tumor cells.

• Pancreatic tumors – A rare tumor called solid pseudopapillary neoplasm lacks E-cadherin staining, helping distinguish it from other pancreatic tumors.

• Hereditary diffuse gastric cancer syndrome – People with a mutation in the CDH1 gene, which controls E-cadherin, are at increased risk for diffuse gastric cancer and lobular breast cancer.

Why is E-cadherin important in a pathology report?

E-cadherin testing is helpful when the type or origin of a tumor is unclear. For example, distinguishing invasive lobular carcinoma of the breast (which typically lacks E-cadherin) from ductal carcinoma (which usually shows E-cadherin) can affect how the diagnosis is reported and may influence treatment decisions. In other types of tumors, loss of E-cadherin may be associated with more aggressive behavior and a higher risk of spreading.

What does E-cadherin loss mean?

When tumor cells lose E-cadherin, they often become more mobile and less tightly attached. This change may allow the cancer to invade nearby tissues and spread to other parts of the body. Loss of E-cadherin is also linked to resistance to some treatments and worse outcomes in some cancers.

Questions to ask your doctor

• Was E-cadherin tested in my tumor?

• What does the result mean for my diagnosis?

• Could this be related to a genetic condition like CDH1 mutation?

• Does the result affect my treatment plan or prognosis?