Stains
Cytokeratins (CK) - general

Author: Nat Pernick, M.D. (see Authors page)

Revised: 4 December 2015, last major update October 2013

Copyright: (c) 2003-2015, PathologyOutlines.com, Inc.

PubMed Search: cytokeratins[title]
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.
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)
Negative Staining
  • Endothelium, mesenchymal cells
Micro Images

Cytokeratin network of cell