Cite this page: Pernick N. Cytokeratins (CK) - general. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/stainsckgeneral.html. Accessed June 4th, 2023.
Definition / general
- Definition: family of water-insoluble intracytoplasmic structural proteins that are the dominant intermediate filament proteins of epithelial and hair forming cells; also present in epithelial tumors
- Within a cell, form a dense network radiating from the nucleus to the plasma membrane
- Act as cytoplasmic scaffold that gives epithelial cells the ability to sustain mechanical and non-mechanical stress
- Keratin intermediate filaments are highly dynamic structures and are reorganized during mitosis and apoptosis; reorganization is mediated by posttranslational phosphorylation, glycosylation, transglutamination and proteolysis, or through interaction with 14-3-3 or other proteins
- Expression depends on cell type and differentiation status
- Over 25 subtypes are defined based on molecular weight (40 to 68 kDa) and isoelectric pH (5 to 8)
- Moll catalog number (Cell 1982;31:11) ranges from 1 (highest molecular weight) to 23 (lowest molecular weight)
- New nomenclature exists (J Cell Biol 2006;174:169)
- Divided into Type I (acidic; CK10, CK12-19, 40-56.5 kDa) and Type II (neutral-basic, CK1-CK8, 53-67 kDa)
- Type I genes are expressed at 17q21.2, type II genes at 12q13.13
- Proteins are obligate heteropolymers with equimolar amounts of type I and type II proteins that form functional filaments, such as CK8/18, CK5/14, CK1/10
- Also divided into low molecular weight (CAM 5.2, 34 beta E11) and high molecular weight (34 beta E12); pankeratin cocktails contain AE1 and AE3 and possibly also CAM 5.2
- Genes are KRT1 for keratin 1, KRT2 for keratin 2, etc.
- Pankeratin: immunohistochemical stain that reacts to a wide range of keratins
Uses by pathologists
- Diagnose epithelial (cytokeratin+) versus nonepithelial cells / tumors (usually cytokeratin negative but there are many exceptions)
- Diagnose particular types of epithelial tumors based on staining patterns of particular cytokeratins - dot like staining is suggestive of neuroendocrine tumors
- In rebiopsies of tumors, don’t assume that all keratin+ cells are residual tumor cells (Am J Surg Pathol 2007;31:390)
- Pathologists generally use a pancytokeratin because it includes a variety of cytokeratins and thus is more sensitive
Negative staining
- Endothelium, mesenchymal cells