Cytokeratin 5/6

Cytokeratin 5/6 (CK5/6) are structural proteins found in certain cell types, including mesothelial cells (which line the chest and abdomen) and some squamous cells. Pathologists detect them using a stain called immunohistochemistry on biopsy tissue to help tell mesothelioma apart from lung adenocarcinoma and other cancers that can look similar under the microscope.

Origin

The word "cytokeratin" combines the Greek "kytos" (cell) with "keratin," the family of filament proteins that give cells structural strength. Moll's catalog (Moll et al., 1982) numbered the human keratins 1 through 20 by size and charge; CK5 and CK6 are two of those subtypes, and antibodies against them became a routine diagnostic tool in surgical pathology in the 1990s.

Significance in Asbestos Context

For a patient whose biopsy is being evaluated for possible mesothelioma, CK5/6 is one of the "positive markers" pathologists rely on. Mesothelioma cells usually stain positive, while lung adenocarcinoma cells usually do not. A diagnosis is almost never made on CK5/6 alone; pathologists use a panel that typically includes calretinin, WT-1, and D2-40 (positive markers for mesothelioma) alongside negative markers like TTF-1, Napsin A, CEA, and Ber-EP4. A clear, well-documented immunohistochemistry panel matters not only for choosing the right treatment but also for any legal claim, because defense experts often challenge whether the tumor is truly mesothelioma versus a metastatic carcinoma.

Example Sentence

The pathology report noted that the tumor cells were strongly positive for CK5/6 and calretinin and negative for TTF-1, supporting a diagnosis of epithelioid mesothelioma.

Related Terms

Immunohistochemistry, Calretinin, WT-1, Mesothelioma, Epithelioid Mesothelioma, Differential Diagnosis

Notes

• Ask your treating physician or pathologist for a copy of the full immunohistochemistry panel, not just the diagnosis line, and confirm which markers were positive and negative.
• CK5/6 is less helpful in distinguishing mesothelioma from squamous cell carcinoma of the lung, since both can stain positive; if squamous cancer is in the differential, additional markers are needed.
• If the diagnosis is uncertain or contested, request a second opinion from a mesothelioma reference center (such as the U.S.-Canadian Mesothelioma Reference Panel) before treatment decisions are finalized.
• Preserve the original biopsy slides and paraffin blocks; these may be needed for additional staining, expert review, or litigation.