CYTOKERATINS

Cytokeratins are a subfamily of intermediate filament proteins and are characterized by a remarkable biochemical diversity, represented in epithelial tissues by at least 20 different polypeptides. They range in molecular weight between 40 kDa and 68 kDa and isoelectric pH between 4.9 – 7.8. The individual cytokeratin polypeptides are designated 1 to 20. Cytokeratin 1 has the highest molecular weight and the highest isoelectric pH, while cytokeratin 19 has the lowest molecular weight and a low isoelectric pH. The cytokeratins are divided into the type I and type II subgroups, the type II family members comprising the basic to neutral cytokeratins 1-8, while the type I group comprises the acidic cytokeratins 9-20. The cytokeratins are expressed in combinations which characterize the type of epithelium.
 

 

Human colon after immunostaining with the cytokeratin 18 antibody RCK106 (A) and cytokeratin 5 + 8 antibody RCK102 (B). Only the epithelial cells stain strongly positive with both cytokeratin antibodies. Fibroblasts and smooth muscle cells are negative.

 


The various epithelia in the human body usually express cytokeratins which are not only characteristic of the type of epithelium, but also related to the degree of maturation or differentiation within an epithelium. In summary the following cytokeratin phenotypes can be distinguished in different types of epithelia:
 
1.   Cuboidial and columnar epithelium, or one-layered epithelium, generally referred to as “simple epithelium”, which is in direct contact with the basement membrane and has a free luminal surface at the apical side of the cell, primarily expresses cytokeratins 8 and 18 and often cytokeratins 7, 19 and 20. The latter three cytokeratins are expressed in certain subtypes of these epithelia.

2.   Stratified epithelia are subdivided into the keratinizing, the non-keratinizing and transitional type. The keratinizing and non-keratinizing epithelia have a basal cell layer which invariably expresses cytokeratins 5 and 14. The suprabasal cell layers express cytokeratins 4 and 13 in noncornifying epithelia and cytokeratins 1 and 10 in cornifying epithelia. The transitional epithelium of the urinary bladder expresses cytokeratins 4 and 13 together with the cytokeratins of the “simple” epithelia i.e. cytokeratins 7, 8, 18, 19 and 20.

3.   Combined epithelia, morphologically characterized by a basal cell layer and a layer of columnar cells both in contact with the basement membrane. The basal cells express cytokeratins 5, 14 and 17, while the luminal cells can express different combinations of cytokeratins 7, 8, 18 and 19.

4.   Squamous epithelia with a high cell turnover express cytokeratins 6 and 16.


Human uterine cervix after double-immunostaining with the cytokeratin 18 antibody RGE53 (A) which recognizes specifically glandular epithelium, and with a broad spectrum cytokeratin antiserum (B) staining both glandular and squamous epithelial cells.

In the field of diagnostic medicine the antibodies against cytokeratins are instrumental in the distinction of epithelial malignancies from sarcomas and lymphomas of various types. Cytokeratin subtype expression patterns are however also being used to an increasing extent in the distinction of different types of epithelial malignancies. The cytokeratin antibodies are not only of assistance in the differential diagnosis of tumours using immunohistochemistry on tissue sections, but are also a useful tool in cytopathology and flow cytometric assays.
 



RCK102 cytokeratin staining of a human squamous cell carcinoma of the lung
 

RGE53 cytokeratin 18 staining of the glandular part of the human uterine cervix
 


RGE53 cytokeratin 18 staining of hepatocytes in human liver
 



RGE53 cytokeratin 18 staining of a human small cell lung carcinoma

 



RCK106 cytokeratin 18 staining of HaCat cells, a human keratinocyte culture