When malignant pleural mesothelioma is suspected, physicians must confirm the diagnosis to prescribe the most effective treatment plan. Cytokeratin 5 and 5/6 are important proteins that help to distinguish malignant mesothelioma from pulmonary adenocarcinoma, the most common type of lung cancer.[1]
What Is Cytokeratin?
Cytokeratin is a type of protein found on epithelial cells, which are the cells that line the inside and outside surfaces of the body. On the outside of the body, cytokeratin helps form the hair, nails, and outer layer of skin. They are the dominant intermediate filament proteins of epithelial and hair-forming cells.
Cytokeratin is also present in epithelial tumors that form on the epithelial cells found inside the body in the lining of the organs, glands, and other body parts.[2] Epithelial cells of the mesothelium are where the rare asbestos-related tumors are first formed.
Twenty different types of cytokeratins have been identified in humans, each with its own unique number. The presence of cytokeratins in higher-than-normal quantities is an indication of malignancy.
Determining the number of a specific type of cytokeratin present can help confirm the type of cancer, distinguish it from other forms of cancer, identify the most appropriate cancer treatment, gauge whether a cancer treatment is effective, and detect whether cancer has recurred. For malignant mesothelioma, Cytokeratin 5, or CK5, has been identified as most helpful.
Cytokeratin 5 is one of the most commonly used immunohistochemical stains in confirming a diagnosis of mesothelioma. Though it is typically present in several different pleural neoplasms, its primary utility lies in distinguishing malignant pleural mesothelioma from pulmonary adenocarcinoma, the most common form of lung cancer.
The use of Cytokeratin 5/6 antibodies detects the presence of Cytokeratin 5 proteins. Their presence distinguishes epithelioid mesothelioma (CK5/6+ in 83%) from lung adenocarcinoma (CK5/6- in 85%), including in pleural effusions (CK5/6+ in 90% mesothelioma, 0% adenocarcinoma).[3]
What Is Immunohistochemistry and How Does it Help Diagnose Mesothelioma?
Immunohistochemistry is a laboratory science that uses antibodies to see whether antigens, substances that cause your immune system to produce antibodies against them, are present and to identify them.
Immunohistochemistry is an essential aspect of confirming a mesothelioma diagnosis, creating the most effective treatment plan, and understanding the most likely outcome of a patient’s disease.[4]
Pathologists are medical doctors who study fluids, tissues, and organs taken from the body. In conducting an immunohistochemistry test, they attach the specific antibody for the antigen that they are seeking to a fluorescent dye.
They then add the antibody to the tissue sample to see whether it attaches to the antigen. When the dye is activated, the pathologist can see whether the antigen is present or not.
Studies have shown that Cytokeratin 5 and Cytokeratin 6 can help distinguish between lung cancer and mesothelioma. Both are dominant in several different types of normal tissues, and both are present in more than 95% of squamous cell carcinomas.
When applying CK5/6 antibodies to mesothelioma and adenocarcinoma cells, the dye is almost always activated when applied to epithelioid mesothelioma cells, and mostly inactive when applied to adenocarcinoma cells.[5]
The Importance of the Correct Diagnosis
Though both malignant pleural mesothelioma and lung cancer are thoracic cancers, the two are very different and require very different treatment protocols.
Both mesothelioma and lung cancer can be caused by exposure to asbestos. Malignant mesothelioma has a unique genetic makeup that makes it particularly aggressive and difficult to treat. Its tumors grow as diffuse masses, while lung cancer tumors tend to grow as individual masses with well-defined boundaries.
Malignant pleural mesothelioma is extremely difficult to diagnose early and accurately. This is one of the reasons why the disease has such a poor prognosis.
Many patients delay seeking treatment, thinking that they have the flu or another respiratory condition. Then, once they seek treatment, they are frequently seen by physicians who have little exposure to this extremely rare form of cancer.
The longer it takes to diagnose mesothelioma, the more advanced the growth of its tumors and the worse the patient’s prognosis.
Understanding whether a tumor is lung cancer or malignant pleural mesothelioma is essential to treatment planning. This is why the use of Cytokeratin 5/6 testing, in combination with testing for other biomarkers, as well as diagnostic imaging, is so important.
The Limitations of Cytokeratin 5/6 Testing
Cytokeratin 5/6 has proven invaluable for distinguishing between epithelioid pleural mesothelioma and adenocarcinoma from cells taken from pleural effusions, but it isn’t perfect. B
Because CK 5/6 is reactive in several other types of epithelial tumors, including squamous cell carcinoma, basal cell carcinoma, thymoma, salivary gland tumors, and biphasic malignant mesothelioma, it is less useful in confirming a diagnosis when those other illnesses are suspected.[1]
Similarly, when CK 5/6 is used to test peritoneal effusions drawn from the abdominal cavity to distinguish between peritoneal mesothelioma and metastatic adenocarcinomas, the latter may also trigger a positive response.[6]
