A cytokeratin stain is a specialized laboratory tool used by pathologists to help identify and classify tumors in a tissue sample. This technique, known as immunohistochemistry, involves applying antibodies designed to bind specifically to a group of structural proteins called cytokeratins, which are found inside cells. When the antibodies attach to the cytokeratins, a visible color change occurs under the microscope, allowing the pathologist to confirm the presence of these proteins. The presence or absence of this staining provides significant clues about a tumor’s origin and lineage, making it a routine procedure in cancer diagnosis.
The Role of Cytokeratins in Epithelial Cells
Cytokeratins are a family of proteins that form intermediate filaments, part of the cell’s cytoskeleton. These filaments provide mechanical strength and structural integrity. Cytokeratins are found almost exclusively in epithelial cells, which line the surfaces of the body, such as the skin, and form the covering of organs and glands.
The expression of specific cytokeratin types within a cell is largely dependent on the type of epithelium and the organ it belongs to. For instance, the cytokeratin profile of a skin cell is different from that of a colon cell. The presence of cytokeratins, therefore, acts as a molecular signature for epithelial tissue.
Identifying Carcinomas Through Staining
The primary function of cytokeratin staining in pathology is to determine if a tumor originated from epithelial cells. A positive stain strongly suggests the tumor is a carcinoma, which is the most common type of cancer, originating from the epithelial lining of an organ. This initial classification is a fundamental step in cancer diagnosis, particularly when a pathologist is examining a poorly differentiated tumor or a metastasis.
The pan-cytokeratin stain, which recognizes a wide range of cytokeratin types, is highly sensitive for nearly all carcinomas. If a tumor stains positive for pan-cytokeratin, it immediately directs the diagnostic workup toward epithelial-derived cancers. Conversely, if a tumor sample does not stain for cytokeratins, it rules out a carcinoma and suggests the tumor likely belongs to another category.
Tumors that are negative for cytokeratin staining include sarcomas, which arise from connective tissues like bone or muscle, and lymphomas, which originate from immune cells. Melanomas, cancers of pigment-producing cells, are also typically negative for cytokeratins. Distinguishing a carcinoma from a sarcoma or lymphoma requires vastly different treatment approaches.
Understanding Specific Cytokeratin Markers
Beyond simply identifying a tumor as a carcinoma, specific cytokeratin markers help pathologists determine the tumor’s site of origin, especially in cases of metastatic disease or cancer of unknown primary. The expression profile of certain cytokeratin subtypes is often retained in the malignant cells, allowing them to trace the cancer back to its original organ.
The combination of Cytokeratin 7 (CK7) and Cytokeratin 20 (CK20) is the most frequently used panel for this purpose. CK7 is typically expressed in epithelial cells of the lung, breast, ovary, and upper gastrointestinal tract, while CK20 is characteristic of cells in the colon, appendix, and urothelium. The resulting four combinations of positive (+) and negative (-) staining provide powerful diagnostic clues.
A tumor staining CK7 positive and CK20 negative (CK7+/CK20-) strongly suggests an origin in the lung, breast, ovary, or thyroid. This pattern is seen in approximately 95% of metastatic lung adenocarcinomas, making it highly indicative of a thoracic or upper-body primary site. In contrast, a CK7 negative and CK20 positive pattern (CK7-/CK20+) is the classic profile for colorectal adenocarcinoma.
CK7/CK20 Dual Positive and Negative Patterns
The dual positive pattern (CK7+/CK20+) is less common but can point toward specific tumor types like urothelial carcinoma (bladder cancer), pancreatic cancer, or mucinous ovarian cancer. The dual negative pattern (CK7-/CK20-) is often seen in certain high-grade tumors like renal cell carcinoma, prostate cancer, or some squamous cell carcinomas, which then require other specialized markers for definitive diagnosis. Other markers, such as CK5/6, are used to specifically identify squamous cell carcinomas and mesotheliomas, which are cancers arising from the protective lining of organs.
Place in Overall Pathological Analysis
Cytokeratin staining is rarely the only test performed on a tumor sample; rather, it serves as the foundation for a larger diagnostic strategy. It is an initial step in a sequential process where a panel of immunohistochemical stains is used to precisely identify the tumor type and origin. Once the cytokeratin stain confirms the epithelial lineage, other non-cytokeratin markers are introduced to refine the diagnosis.
For example, a tumor confirmed as a carcinoma by a positive cytokeratin stain might then be tested for markers like vimentin, S-100, or CD markers, which are associated with sarcomas, melanomas, or lymphomas, respectively. If the carcinoma is CK7+/CK20-, pathologists will then use organ-specific markers such as TTF-1 for lung or GATA-3 for breast to pinpoint the primary site.