CK 5/6

CK 5/6

Immunohistochemical expression

See Cytokeratins in normal epithelia and specific cytokeratins in common carcinomas.

 

adenocarcinoma

mesothelioma

Clover 19974

5/27

23/23

Ordonez 19985

14/123

40/40

Cury 20001

9/63

56/61

Kayser 20012

72/146

90/118

Carella 20013

1/20

40/46

Atanoos 200110

not studied

51/92

Kaufmann11

30/141

14/14

Miettinen 200110

not studied

22/30

Tot 2001

6/79

9/14

Abutaily 20029

2/35

26/41

 

Chu 200215

1/21

13/17

Miettinen 20038

25/254

26/28

Ordonez 200313

1/50

 

60/60

Overall

17% (166/959)

80% (470/584)

A systematic review of eight studies (consisting of 402 epithelioid mesotheliomas and 402 pulmonary adenocarcinomas) reported sensitivities and specificities of CK5/6 for epithelioid mesothelioma of 83% and 85%16.

Most studies compare mesothelioma with pulmonary adenocarcinoma. There are relatively few studies breaking down pulmonary adenocarcinomas by subtype, or of other types of pulmonary tumour.

adenocarcinoma

acinar type, differentiated

17/146 8

acinar type, solid, poorly-differentiated, mucin-positive

7/49 8

bronchoalveolar, mucinous

0/6 8

bronchoalveolar, non-mucinous

1/7 8

acinar with focal neuroendocrine differentiation

0/22 8

neuroendocrine

0/18 8

clear cell

0/6 8

NOS

3/2914, 1/1117

large cell

NOS

67/120 8, 1/917

with focal neuroendocrine differentiation

3/10 8

neuroendocrine carcinoma

6/33 8

small cell carcinoma

11/41 8, 0/1515, 2/1317

squamous cell

keratinising

62/62 8

non-keratinising

54/62 8

NOS

27/3614, 12/1217

sarcomatoid carcinoma, spindle cell

1/6 8

giant cell carcinoma

3/6 8

poorly differentiated carcinoma

1/314

carcinoid

1/1015

 

Some metastatic carcinomas, such as renal cell carcinoma, pose particular problems.

 

Extra-pulmonary tumours:

 

Adenocarcinomas are mostly negative:

stomach

0/1515

 

colon

0/1612, 3/5314, 0/2015

cholangiocarcinoma

2/1415

pancreas

5/1315

kidney

0/912, 0/1915

breast

1/512, 14/6314, 8/2615

uterus

1/312, 5/1015

ovary

1/212, 12/4414, 6/2415

prostate

7/6414, 0/1815

thyroid

0/212

     

squamous carcinomas

25/2515

basal cell carcinoma of skin

20/2015

hepatocellular carcinoma

1/2815

thymoma

8/815

salivary gland, all types

26/2815

thyroid, all types

0/5415

transitional cell carcinoma of bladder

15/2415

undifferentiated carcinoma, multiple sites

2/2715

adrenocortical tumour

0/2015

germ cell tumour

0/1415

epithelioid sarcoma of soft tissue

0/1215

synovial sarcoma

0/615

   
     
     

Diagnostic utility

 

benign

malignant

 

CK5/6

34bE12

CK5/6

34bE12

negative

0/306

4/306

12/126

12/126

 

positive

<50% of glands

0/306

5/306

0/126

0/126

50-75% of glands

1/306

9/306

0/126

 0/126

75-95% of glands

0/306

10/306

0/126

 0/126

>95% of glands

29/306

2/306

0/126

 0/126

 

CK5/6, unlike LP34, does not produce weak staining of luminal cells and therefore it is easier to identify acini showing two layers of cells in lobular atrophy11. However, the staining is slightly weaker than for LP34 and intermittent in benign acini11. Staining is strengthened by increasing the time of antigen retrieval11. CK5/6 may be superior for differentiation adenocarcinoma from lobular atrophy, while LP34 may be superior in the distinction of adenocarcinoma from PIN11.

References

1 Cury, P. M.,et al. Value of the mesothelium-associated antibodies thrombomodulin, cytokeratin 5/6, calretinin, and CD44H in distinguishing epithelioid pleural mesothelioma from adenocarcinoma metastatic to the pleura. Mod Pathol 2000;13:107-12.

2 K Kayser et al. Glyco- and immunohistochemical refinement of the differential diagnosis between mesothelioma and metastatic carcinoma and survival analysis of patients. J Pathol 2001;193:175-180.

3 Carella R et al. Immunohistochemical panels for differentiating epithelial malignant mesothelioma from lung adenocarcinoma. Am J Surg Pathol 2001;25:43-50.

4 Clover, J., Oates, J., Edwards, C. Anti-cytokeratin 5/6: a positive marker for epithelioid mesothelioma. Histopathology 1997;31:140-143.

5 Ordonez, N. G. (1998). "Value of cytokeratin 5/6 immunostaining in distinguishing epithelial mesothelioma of the pleura from lung adenocarcinoma." Am J Surg Pathol 22(10): 1215-21.

6 Abrahams, N.A., Ormsby, A.H. and Brainard, J. Validation of cytokeratin 5/6 as an effective substitute for keratin 903 in the differentiation of benign from malignant glands in prostate needle biopsies. Histopathology 2002;41:35-41.

7 Moll, R., Dhouailly, D. and Sun, T.T. Expression of keratin 5 as a distinctive feature of epithelial and biphasic mesotheliomas. An immunohistochemical study using monoclonal antibody AE14. Virchows Arch B Cell Pathol Incl Mol Pathol 1989;58:129-45.

8 Miettinen, M. and Sarlomo-Rikala, M. Expression of calretinin, thrombomodulin, keratin 5, and mesothelin in lung carcinomas of different types: an immunohistochemical analysis of 596 tumors in comparison with epithelioid mesotheliomas of the pleura. Am J Surg Pathol 2003;27:150-8.

9 Abutaily, A.S., Addis, B.J. and Roche, W.R. Immunohistochemistry in the distinction between malignant mesothelioma and pulmonary adenocarcinoma: a critical evaluation of new antibodies. J Clin Pathol 2002;55:662-8.

10 Miettinen, M., J. Limon, et al. (2001). "Calretinin and other mesothelioma markers in synovial sarcoma: analysis of antigenic similarities and differences with malignant mesothelioma." Am J Surg Pathol 25(5): 610-7.

11 Freeman, A., K. Treurnicht, et al. (2002). "A comparison of basal cell markers used in the prostate." Histopathology 40(5): 492-4.

12 Jerome 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.

13 Kaufmann, O., E. Fietze, et al. (2001). "Value of p63 and cytokeratin 5/6 as immunohistochemical markers for the differential diagnosis of poorly differentiated and undifferentiated carcinomas." Am J Clin Pathol 116(6): 823-30.

14 Reis-Filho JS, Simpson PT, Martins A, Preto A, Gartner F,Schmitt FC Distribution of p63, cytokeratins 5/6 and cytokeratin 14 in 51 normal and 400 neoplastic human tissue samples using TARP-4 multi-tumor tissue microarray. Virchows Arch 2003; 443:122-32 This study used tissue microarrays.

15 Chu PG,Weiss LM Expression of cytokeratin 5/6 in epithelial neoplasms: an immunohistochemical study of 509 cases. Mod Pathol 2002; 15:6-10

16 King JE, Thatcher N, Pickering CA, et al. Sensitivity and specificity of immunohistochemical markers used in the diagnosis of epithelioid mesothelioma: a detailed systematic analysis using published data. Histopathology 2006; 48:223-32

17 Johansson L Histopathologic classification of lung cancer: Relevance of cytokeratin and TTF-1 immunophenotyping. Ann Diagn Pathol 2004; 8:259-67

 

This page last revised 16.2.2006.

©SMUHT/PW Bishop