Cytokeratins – markers in tumour diagnostics

Cytokeratins (CKs), the largest family of intermediate filament proteins, are expressed in epithelial and epithelia-deri­ved cells. Unique combinations of type I (acidic, CK9-CK23) and type II (basic, CK1-CK8) cytokeratins serve as specific markers that distinguish different epithelial cell types. Determination of cytokeratine con­tent has also become an important tool in classification of tumour cells. The patterns of cytokeratins of a given type of carcinoma appear to be identical in primary tumours and metastases, independent from the specific location and size.
 
Detection of CK5 can be used for distinction between mesotheliomas and most adenocar­cinomas. Certain defects in CK5 lead to inherited skin disorders such as EBS (epidermolysis bul­losa simplex) or DDD (Dowling-Deogs disease). CK7 can serve e.g. as a marker to distinguish between ovarian and gastrointestinal carcinomas, or between transitional cell carcinomas and prostate cancer. Aberrant expression of CK7 in hepatocytes is a marker primary biliary cirrhosis. CK8 and CK18 are hallmark of simple epithelia. Despite structural role, they have signaling function in modulation of cell attachment, protein synthesis and G1/S phase transition and are involved in stress adaptation. CK18 is also used as a serum biomarker for monitoring therapy-induced tumour apoptosis and necrosis. Detection of CK10, CK13 and CK17 can be used in squamous cell carcinoma diagnos­tics. Monitoring of CK19 expression is important for prognosis of various tumours. The expression of CK19 may be linked to retention of undifferentiated cell character.
 
Fig. 1: Distribution of cytokeratins in Hep-2 cells as detected using pan-cytokeratin antibody C-11.
 
 
Expression of cytokeratins in selected human carcinoma types:

 

 
Fig. 2: Expression of cytokeratin 10 in human skin basaliom, as detected on paraffin-embedded sections using antibody clone VIK-10.
 
Anti-cytokeratin antibodies in our portfolio:

 
 

 
Fig. 3: Expression of cytokeratin 19 in human liver, as detected on paraffin-embedded sections using antibody clone A53-B/A2 (green). Cell nuclei stained with PI (orange).
 
 
 
Further reading:
Moll R et al.: Cell 1982;31:11-24.   Varadhachary GR et al.: Cancer 2004;100:1776-1785.   Gusterson BA et al.: Breast Cancer Res. 2005;7:143-148.   Kanaji N et al.: Lung Cancer 2007;55:295-302.   Moll R et al.: Virchows Arch. B Cell Pathol. Incl. Mol. Pathol. 1989;58:129-145.   Rugg EL et al.: J. Invest. Dermatol. 2007;127:574-580.   Betz RC et al.: Am. J. Human Genet. 2006;78:510-519.   Ramaekers F et al.: Am. J. Pathol. 1990;136:641-655.   Yabushita K et al.: Liver 2001;21:50-55.   Chatzipantelis P et al.: Hepatol. Res. 2006;36:182-187.   Galarneau L et al.: Exp. Cell Res. 2007;313:179-194.   Ku NO and Omary MB: J. Cell Biol. 2006;174:115-125.   Lau AT and Chiu JF: Cancer Res. 2007;67:2107-2113.   Linder S et al.: Cancer Lett. 2004;214:1-9.   Maddox P et al.: J. Clin. Pathol. 1999;52:41-46.   Toyoshima T et al.: J. Cancer Res. Clin. Oncol. 2008;134:515-521.   Deshpande V et al.: Am. J. Surg. Pathol. 2004;28:1145-1153.   Park YJ et al.: J. Korean Med. Sci. 2007;22:621-628.   Barroeta JE et al: Endocr. Pathol. 2006;17:225-234.   Lindberg K and Rheinwald JG; Am. J. Pathol. 1989;134:89-98.
 
 

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