Cytokeratins are proteins that form the internal scaffolding, or cytoskeleton, in epithelial cells. These filaments provide mechanical strength and structure to the cells lining the body’s surfaces and cavities. Staining is a laboratory technique that uses specialized dyes to highlight cellular components for microscopic examination. A cytokeratin stain is a method designed to specifically detect these cytokeratin proteins inside cells through a process called immunohistochemistry.
Primary Uses of Cytokeratin Stains
The primary function of a cytokeratin stain in pathology is to determine a cell’s origin, which helps in diagnosing and classifying diseases like cancer. The stain is used to identify tumors that arise from epithelial cells, known as carcinomas, which are the most common category of malignant tumors. This helps distinguish carcinomas from other types of cancers, such as sarcomas, lymphomas, or melanomas, as these other tumor types do not stain for cytokeratins.
This identification is valuable for metastatic cancer, where cancer cells have spread from their original location. A pathologist may encounter a tumor in an organ like the liver or lung composed of cells that are not native to that location. Using a cytokeratin stain, they can confirm if the foreign cells are epithelial in origin, suggesting the tumor is a metastasis from a primary carcinoma. Pinpointing the cell type helps narrow down potential primary tumor sites and influences treatment strategies.
The Cytokeratin Staining Process
The process begins with a tissue sample, obtained from a biopsy or surgical procedure, which is thinly sliced and mounted onto a glass slide. This preparation preserves the tissue’s structure and makes the cells accessible for analysis. The method involves using antibodies, which are proteins engineered to recognize and bind to a specific target—in this case, cytokeratin proteins.
Primary antibodies are applied to the tissue on the slide. If cytokeratin proteins are present within the cells, the antibodies will attach to them. To make this binding visible, a secondary antibody is applied that is designed to bind to the primary antibody. This secondary antibody is linked to an enzyme that produces a distinct color, often brown or red, when a chemical substrate is added.
When a pathologist views the slide under a microscope, the cells containing the cytokeratin proteins will appear colored, while cells that lack these proteins will not. This color change provides a clear visual signal, pinpointing which cells are expressing cytokeratins. The specific location and intensity of the staining provide additional information for the diagnostic process.
Conditions Detected by Cytokeratin Stains
There are over 50 different types of cytokeratin proteins, and various epithelial tissues express unique combinations of them. This specificity is retained when these tissues become cancerous, allowing pathologists to use panels of cytokeratin stains to learn more about a tumor. This detailed profiling helps create a “fingerprint” of the tumor, which can distinguish between possibilities that may look identical under a standard microscope.
Different cytokeratin profiles help classify carcinoma subtypes. For example, some cytokeratins are found in glandular cells that form adenocarcinomas, while others are characteristic of squamous cells that form squamous cell carcinomas. Staining for specific cytokeratins like CK7 and CK20 is useful in determining the origin of a metastatic tumor.
A tumor that is positive for CK7 and negative for CK20 might suggest a primary cancer of the lung, breast, or ovary. Conversely, a tumor that is negative for CK7 and positive for CK20 is highly characteristic of colorectal adenocarcinoma. This information provides a more precise diagnosis for planning effective treatment.
Interpreting Cytokeratin Stain Outcomes
A pathologist interprets the cytokeratin stain results in the context of the patient’s overall medical picture. A “positive” result signifies that the targeted cytokeratin proteins were detected, which is visualized as a colored stain. This finding supports the conclusion that the cells are epithelial in nature. A “negative” result means the cells did not contain the specific cytokeratin being tested for.
Pathologists evaluate more than just the presence or absence of a stain; they also assess the pattern and intensity. For example, staining might be diffuse throughout the cell’s cytoplasm or concentrated in a particular area. The strength of the color can also provide clues. A cytokeratin stain is one piece of a larger diagnostic puzzle.
The final diagnosis is never based on this single test alone. The pathologist integrates the staining results with the appearance of the cells (morphology), information from other laboratory tests, and the patient’s clinical history. This comprehensive approach ensures an accurate diagnosis, as the meaning of a positive or negative result can change depending on the clinical situation.