When malignant pleural mesothelioma is suspected, physicians need to confirm the diagnosis so that they can prescribe the best possible 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 of 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, and each has its own number. The presence of cytokeratins in higher-than-normal quantities is an indication of malignancy, and determining how many of a specific type of cytokeratin are present can help to confirm the type of cancer; distinguish it from other forms of cancers; identify the most appropriate cancer treatment gauge whether a cancer treatment is working; and detect whether cancer has come back. 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 malignant pleural 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 what the antigen is. 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.
When it comes to testing cancer cells to see whether they are lung cancer or malignant mesothelioma, studies[5] have shown that Cytokeratin 5 and Cytokeratin 6 are both dominant in several different types of normal tissues and that both are present in more than 95% of squamous cell carcinomas, but when applying CK5/6 antibodies on mesothelioma and adenocarcinoma cells, the dye is almost always activated when applied to epithelioid mesothelioma cells, and mostly inactive when applied to adenocarcinoma cells.
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.
Though 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, and 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, and 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 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 biphasis 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]
