Written by Karen Selby, RN | Medically Reviewed By Dr. Jeffrey Velotta | Edited By Walter Pacheco | Last Update: November 14, 2024

What Is Cytokeratin 5 and 5/6?

Cytokeratin 5 mesothelioma cells under microscope

Cytokeratins are keratin proteins in epithelial tissue. This tissue lines the outer surfaces of organs and blood vessels. They provide epithelial cells with structural support.

Cytokeratins are numbered based on where they are in the body. Cytokeratin 5 lives in the cells on the outermost layer of skin in humans and animals. The KRT5 gene encodes it, which pairs with type I keratin K14.

Cytokeratin 5 is a key biomarker for mesothelioma, breast cancer and lung cancer. It also helps to tell squamous carcinomas apart from adenocarcinomas.

Pathologists use cytokeratin 5 to distinguish mesothelioma from adenocarcinoma, the most common type of lung cancer. They do this by staining tissue samples with cytokeratin 5/6, an antibody that detects cytokeratins 5 and 6.

Cytokeratin 5/6 cannot identify cancerous mesothelioma on its own. Pathologists use several immunohistochemical markers when diagnosing cancer.

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Cytokeratin 5 and 5/6 in Diagnosing Mesothelioma

Cytokeratin 5/6 mesothelioma cells under microscope

Cytokeratin 5/6 is a positive marker for pleural mesothelioma in over 75% of cases. It is also present in certain types of lung cancers and breast cancers. Pathologists use cytokeratin 5/6 to stain cancer tissue samples.

Many doctors misdiagnose pleural mesothelioma as lung cancer. This is mainly if the tumors have spread to other parts of the body.

Pathologists can use cytokeratin 5/6 to identify tumor cells. With rare exceptions, epithelial mesothelioma is the only tumor with glandular morphologic features that shows cytokeratin 5/6.

Cytokeratin 5/6 is rarely found in lung adenocarcinomas. If a tumor sample shows high levels of it, it likely indicates mesothelioma. This suggests it is not metastatic adenocarcinoma.

However, this marker is not practical for all cell types of mesothelioma. Cytokeratin 5/6 staining is usually weak or negative for sarcomatoid mesothelioma. This cell type is the least common and hardest to treat.

It is also ineffective in distinguishing between pleural mesothelioma and squamous cell carcinomas, which account for about 25% to 30% of all lung cancers.

Mesothelioma Research Studies Involving Cytokeratin 5/6

Several studies have tested cytokeratin 5/6 as a marker for malignant mesothelioma.

Cytokeratin and p63 are useful for finding cancers of unknown origins. A 2001 study in the American Journal of Clinical Pathology showed this. It involved 14 cases of malignant mesothelioma.

Both cytokeratin 5/6 and calretinin are markers for mesothelioma in effusion samples. Effusion, or excess fluid buildup, is a common symptom of pleural and peritoneal mesothelioma.

Cytokeratin 5/6 staining was present in the study in 33 of 34 mesothelioma cases. At the same time, only six of 67 adenocarcinomas were positive for the protein.

The study noted cytokeratin 5/6 staining may be less useful for peritoneal effusion specimens. Metastatic adenocarcinomas are more likely to express the marker in the abdomen.

A 2002 study in Modern Pathology warned against using cytokeratin 5/6 to differentiate mesothelioma from metastatic adenocarcinoma. The study found that many nonpulmonary adenocarcinomas may be positive for cytokeratin 5/6. Pathologists must rely on other markers as well.

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