3 Min Read
Last Updated: 06/05/2024
Fact Checked

Written by Karen Selby, RN | Medically Reviewed By Dr. Jeffrey Velotta | Edited By Walter Pacheco

Fact Checked

What Is Cytokeratin 5 and 5/6?

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

The different types of cytokeratins get numbered based on their location in the body.

Cytokeratin 5 mesothelioma cells under microscope

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 has become an important biomarker for different types of cancer, including mesothelioma, breast cancer and lung cancer. CK5 has characteristics that help differentiate squamous carcinomas 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 is a positive marker for malignant pleural mesothelioma in over three-fourths 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.

Cytokeratin 5/6 mesothelioma cells under microscope

Many doctors misdiagnose pleural mesothelioma as lung cancer, mainly if tumors have spread beyond the point of origin to other parts of the body.

Pathologists can differentiate tumor cells using immunohistochemical markers such as cytokeratin 5/6. With rare exceptions, epithelial mesothelioma is the only tumor with glandular morphologic features that shows cytokeratin 5/6.

Cytokeratin 5/6 immunoreactivity is rare in lung adenocarcinomas. If a tumor sample shows strong expression of cytokeratin 5/6, it gives pathologists a hint that the tumor is malignant mesothelioma rather than a 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, the least common and hardest-to-treat cell type of asbestos-related cancer.

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 evaluated cytokeratin 5/6 as a diagnostic marker for mesothelioma.

Cytokeratin and p63 are effective in differentiating cancers of unknown primary sites. A 2001 study in the American Journal of Clinical Pathology showed this fact. The study included 14 malignant mesotheliomas.

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 tested positive for the protein.

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

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

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