Epithelial cells form the network of tissues that line the surfaces and cavities of the body. From the outermost layer of the skin to the inner linings of organs, these cells act as a protective barrier and perform specialized functions like secretion and absorption. To identify these cells, scientists rely on specific molecules they produce, known as cell markers.
Cell markers are proteins and carbohydrates on or within a cell that reveal its type and tissue of origin. An epithelial cell marker is a specific molecule that signals a cell belongs to an epithelial tissue. This system of molecular identification helps classify cells, forming a foundation for understanding both normal tissue structure and disease.
The Role of Markers in Identifying Epithelial Tissues
The body’s diverse epithelial tissues are not distinguished by a single, universal marker but by unique combinations of them. Different types of epithelia, such as those in the lungs versus the colon, express distinct sets of proteins that reflect their specific functions. This variation allows for the precise identification of a tissue’s source.
A prominent family of proteins used for this purpose is the cytokeratins (CKs). Cytokeratins are structural proteins that form the internal scaffolding of epithelial cells, and different epithelial tissues assemble this scaffolding from different CK building blocks. For example, some cytokeratins are common in lung tissue while others are found in the colon. This differential expression creates a “staining profile” that acts as a molecular fingerprint for a given tissue, which pathologists can analyze to confirm its identity.
Application in Disease Diagnosis
The ability to identify a tissue’s origin becomes important in the context of cancer. When cancer cells spread from their original location to other parts of the body, a process known as metastasis, they retain the molecular markers of the primary tumor. This allows pathologists to trace a metastatic tumor back to its source, an important step in planning treatment.
This application is evident in cases of “cancer of unknown primary” (CUP), a diagnosis given when a metastatic tumor is found, but the original cancer site cannot be located. In these cases, cytokeratin profiles become a diagnostic tool. For instance, if a tumor of epithelial origin is found in the liver, determining its CK7/CK20 profile can help narrow down the possibilities. A CK7-negative/CK20-positive pattern suggests the cancer originated in the colon, while a CK7-positive/CK20-negative pattern points toward a primary tumor in the lung, breast, or ovary.
Beyond the cytokeratins, other markers provide broader information. The Epithelial Cell Adhesion Molecule (EpCAM) is a protein on the surface of most normal epithelial cells. Many cancers that arise from these tissues, known as carcinomas, continue to express EpCAM at high levels. Its presence makes EpCAM a general marker for confirming that a tumor is of epithelial origin.
Markers in Cancer Progression and Treatment
Beyond initial diagnosis, epithelial markers provide insights into a cancer’s behavior and can guide therapeutic decisions. The presence or absence of certain markers can signal how a tumor is likely to progress. This is illustrated by a cellular process known as the Epithelial-to-Mesenchymal Transition (EMT), which is associated with increased cancer cell mobility and invasion.
During EMT, cancer cells shed their epithelial characteristics to adopt traits of more migratory cells. A primary event in this transition is the loss of E-cadherin, a protein that helps epithelial cells adhere to one another. When cancer cells lose E-cadherin, their connections weaken, allowing them to detach from the primary tumor and metastasize. Observing the loss of E-cadherin can indicate a more aggressive cancer.
Furthermore, some markers are direct targets for treatment. The EpCAM protein is a target for certain cancer therapies because it is highly expressed on the surface of many carcinoma cells but less accessible on normal tissues. Antibody-based therapies have been developed to recognize and bind to EpCAM, delivering cytotoxic agents to cancer cells or flagging them for destruction by the immune system.
Laboratory Techniques for Detection
To analyze these molecular markers, scientists employ several laboratory techniques. The most common method is Immunohistochemistry (IHC), which allows for the localization of markers within a preserved tissue sample. In IHC, a thin slice of tissue is incubated with antibodies engineered to bind to a single target marker.
These antibodies are linked to a colored tag that is left behind when the antibody attaches to its target protein. Under a microscope, stained cells reveal the marker’s presence and location. While IHC is excellent for analyzing solid tissues, other methods are used for different sample types.
Flow cytometry is used to analyze cells in a liquid suspension, such as blood or bone marrow. In this technique, cells are tagged with fluorescent antibodies and passed through a laser beam for rapid counting and sorting. Another technique, the Western blot, measures the total amount of a specific marker protein within a tissue sample, providing quantitative data.