The Cytokeratin 5/6 (CK5/6) marker is a specific protein used in medical diagnostics, often appearing in complex pathology reports. A “CK5/6 Positive” result indicates the presence of this protein within a tissue sample. This finding is a piece of the diagnostic puzzle, providing pathologists with directional information about the origin of cells, particularly those that may be abnormal. Understanding the biological role of CK5/6 and the detection technique helps demystify this common phrase in pathology.
The Biology of Cytokeratin 5/6
Cytokeratins (CKs) are a family of fibrous proteins that function as the building blocks for the internal scaffolding, or intermediate filaments, within epithelial cells. These proteins provide structural support and mechanical stability to cells that line organs and form protective barriers throughout the body. Cytokeratin 5 (CK5) and Cytokeratin 6 (CK6) are two related types of these proteins frequently analyzed together in diagnostic settings.
CK5 and CK6 are typically found in the basal and lower layers of stratified squamous epithelium, such as the skin, lung lining, and cervix. CK5 is concentrated in the basal cell layer, often pairing with Cytokeratin 14 to create the structural network. CK6 is usually expressed in the suprabasal layers and is often associated with hyperproliferative (rapidly growing) cells. The presence of these combined markers signals cells that originate from or are differentiating toward a squamous or basal cell lineage.
How Pathologists Use Immunohistochemistry
To determine if a sample is “CK5/6 positive,” pathologists use a laboratory technique called Immunohistochemistry (IHC). This method allows for the visualization of specific proteins directly within a prepared tissue sample, typically obtained through a biopsy. The process begins by applying a specialized antibody designed to bind only to the CK5/6 proteins present in the tissue.
The primary antibody is then bound by a secondary antibody tagged with a color-producing enzyme. If CK5/6 is present, the enzyme reacts with an added substrate, causing a visible color change, often a brown or red stain, under the microscope. A “positive” result confirms the presence and location of the CK5/6 protein in the examined cells. Conversely, a “negative” result means the antibody did not bind the protein, and no color change was observed.
What a CK5/6 Positive Result Indicates
A CK5/6 positive result provides a clue to the cell’s identity, suggesting a basal or squamous epithelial origin. This marker is valuable in oncology for classifying tumors of unknown origin, a process called differential diagnosis. Positivity helps narrow down possibilities by indicating the fundamental cell type from which the malignancy arose.
One of the most common applications is distinguishing between lung cancers, specifically Squamous Cell Carcinoma (SCC) and Adenocarcinoma (ADC). SCCs arise from the squamous lining of the airways and are strongly CK5/6 positive, while ADCs arise from glandular cells and are usually CK5/6 negative. This difference in protein expression guides the pathologist in correctly classifying the tumor subtype, which is necessary for determining the appropriate treatment plan.
CK5/6 is also a widely used marker for diagnosing Mesothelioma, a cancer of the lining around the lungs (pleura) or abdomen (peritoneum). Epithelioid Mesothelioma cells are consistently positive for CK5/6, which helps distinguish them from metastatic Adenocarcinoma in the same region, which is typically negative. Finding this marker in a pleural biopsy supports a mesothelial cell origin. Furthermore, in breast pathology, CK5/6 positivity can indicate a “basal-like” molecular subtype of breast cancer, influencing prognosis and therapeutic approaches.
Interpreting Results in a Diagnostic Panel
A single positive result for CK5/6 is rarely sufficient for a final diagnosis; it serves as one piece in a larger analytical matrix. Pathologists rely on a “panel” of immunohistochemical markers, testing the tissue for several different proteins simultaneously to build a comprehensive cell profile. The entire pattern of positive and negative results dictates the final classification of the cells.
To confirm a diagnosis of lung SCC, the pathologist looks for CK5/6 and p63 positivity, combined with negativity for adenocarcinoma markers like TTF-1 and Napsin A. Conversely, a positive result for CK5/6 alongside positive staining for Calretinin and WT1 strongly suggests Mesothelioma. This layered approach is necessary because many different tumor types can express this protein, and the combination of markers provides the specificity needed for an accurate diagnosis.