Cytokeratin 20

This cytokeratin is distantly related to other acidic (type I) keratins. It was formerly known as "protein IT".

Reliable demonstration in paraffin sections requires antigen retrieval by pressure cooking.

Immunohistochemical expression

This cytokeratin is expressed by:

•  Gastrointestinal epithelium and gastrointestinal carcinomas

• Urothelium and transitional cell carcinomas: usually CK7+/CK20+

• Colorectal carcinoma

• Gastric carcinoma, less reliably positive

• Some adenocarcinomas of the biliary tree and pancreatic duct

• Mucinous ovarian adenocarcinoma

Breast, ductal carcinoma	5/11926, 11/107 (immunostaining histoscore >10)10
Breast, lobular carcinoma	0/1026
Lung adenocarcinomas	3/3526
Gastric adenocarcinomas	20/3926
Small intestinal adenocarcinoma	very limited data; 2/2 cases3
Colonic adenocarcinoma	21/2526, 82/94 (immunostaining histoscore >10)10
Pancreatic adenocarcinoma	9/2626
Ovarian adenocarcinoma (non-mucinous)	0/2926, 0/299
Endometrial adenocarcinoma	0/163
Renal adenocarcinomas	0/4526, 2/613

• Rarely in islet cell tumours: 1/7 cases³

• Transitional cell carcinoma: 24/33 cases³, 13/19 pure transitional cell carcinomas⁶, 16/19 transitional cell carcinomas with focal squamous metaplasia⁶.

• Merkel cell carcinoma (punctate globular inclusion-like or perinuclear pattern of staining)

• Small cell carcinoma of the salivary gland

• Small intestinal carcinoids; 6/7 cases³

• Prostate: 10/36 cases³

• Some mesothliomas: 18/40⁷

Generally not expressed by:

• Small cell carcinomas, other than those of the salivary gland and Merkel cell tumours

• Squamous cell carcinomas of the

  • lung: 0/39 cases³
    
  • larynx: 0/32 cases³
    
  •  bladder: 0/4 cases⁶
    
  • uterine cervix: 0/17 cases³

• Thyroid tumours:

  • follicular adenoma: 0/17 cases³

  • follicular carcinoma: 0/10 cases³

  • papillary carcinoma: 0/30 cases³

• Seminoma: 0/30 cases³

• Thymoma: 0/29 cases ³

Where the subject has been examined, there is concordance in the expression of cytokeratin 20 between primary carcinomas and their lymph node metastases.⁵

Diagnostic utility

• The coordinate expression of cytokeratins 7 and 20 is particularly useful in identifying the primary site of a carcinoma.

• It is useful in the differential diagnosis of small cell carcinomas:

Site of small cell carcinoma (Number of cases)	Number showing CK20 reactivity	Number showing CAM 5.2 or MNF-16 staining
Merkel cell tumour	98% (33/34, 23/234)	88% (30/34)
Lung	1% (1/37, 0/524)	35% (13/37)
Salivary	3/5	3/5
Alimentary tract	0/9, 0/154	4/9
Upper aerodigestive tract	0/5	3/5
Larynx	0/9	2/9
Pancreas	0/1	0/1
Thymus	0/3	1/3
Breast	0/2	0/2
Kidney	0/1	0/1
Urinary bladder	0/2, 0/34	0/2
Prostate	0/3, 0/34	0/3
Uterine corpus	0/1	0/1
Uterine cervix	1/11	1/11

References

Chan JKC et al.  Cytokeratin 20 immunoreactivity distinguishes Merkel cell (primary cutaneous neuroendocrine) carcinomas and salivary gland small cell carcinomas from small cell carcinomas of various sites.  Am J Surg Pathol 1997;21:226-34

Adv Anat Pathol 1997;4:261-2.

³Miettinen M. Keratin 20: immunohistochemical marker for gastrointestinal, urothelial and Merkel cell carcinomas. Mod Pathol 1995;8:384-388.

⁴Cheuk W et al. Immunostaining for thyroid transcription factor-1 and cytokeratin 20 aids in the distinction of small cell carcinoma from Merkel cell carcinoma, but not pulmonary from extrapulmonary small cell carcinoma. Arch Pathol Lab Med 2001;125:228-231.

⁵Jiang et al. Cytokeratin 7 and cytokeratin 20 in primary urinary bladder carcinoma and matched lymph node metastasis. Arch Pathol Lab Med 2001;125:921-3.

⁶Harnden, P., Southgate, J. Cytokeratin 14 as a marker of squamous differentiation in transitional cell carcinomasJ Clin Pathol 1997;50:1032-3.

⁷Garcia-Prats, M. D., C. Ballestin, et al. (1998). "A comparative evaluation of immunohistochemical markers for the differential diagnosis of malignant pleural tumours." Histopathology 32(5): 462-72.

⁸Jerome Marson, V., J. Mazieres, et al. (2004). "Expression of TTF-1 and cytokeratins in primary and secondary epithelial lung tumours: correlation with histological type and grade." Histopathology 45(2): 125-34.

⁹Kaufmann, O., T. Deidesheimer, et al. (1996). "Immunohistochemical differentiation of metastatic breast carcinomas from metastatic adenocarcinomas of other common primary sites." Histopathology 29(3): 233-40.

¹⁰Lagendijk, J. H., H. Mullink, et al. (1999). "Immunohistochemical differentiation between primary adenocarcinomas of the ovary and ovarian metastases of colonic and breast origin. Comparison between a statistical and an intuitive approach." J Clin Pathol 52(4): 283-90.

©SMUHT/PW Bishop