Coordinate expression of cytokeratins 7 and 20

Specific cytokeratin expression gives valuable information as to the primary site of a carcinoma. Cytokeratins 7 and 20 are most useful in this respect.

(When we are trying to determine the line of differentiation of a tumour, we not uncommonly are forced to rely on very limited immunoreactivity as the best available evidence. This is not appropriate when evaluating specific cytokeratins. It is important to know the thresholds for positivity, which vary between papers, in some cases the threshold being set as low as 1% of cells1,7, often at 10% of cells, but at the most stringent requiring at least 50% of cells to show at least moderate staining2.)

 

Predominantly CK7+/CK20-

 

CK7+/CK20+

CK7+/CK20-

CK7-/CK20+

CK7-/CK20-

Lung, adenocarcinoma

14% (6/541, 6/742, 2/155, 2/438, 1/1010, 1/2122, 18/4224)

76% (39/541, 64/742, 12/155, 16/176, 41/438, 9/1010, 20/2122, 14/1623, 24/4224, 30/4025)

0/541, 0/742, 0/155, 0/1010

10% (9/541, 4/742, 1/155, 0/1010, 2/1623, 10/4025)

Lung, bronchoalveolar

0/31, 8/288

3/31, 20/288

0/31

0/31

Malignant mesothelioma

0/161, 0/1710

11/161, 11/1710

0/161, 0/1710

5/161, 6/1710

Breast, infiltrating ductal

6/381, 0/2010

31/381, 19/2010, 6/622, 6/1225

1/381, 0/2010

0/381, 1/2010, 6/1225

Breast, infiltrating lobular

1/111, 0/610

10/111, 6/610

0/111, 0/610

0/111, 0/610

Thyroid neoplasms

0/5510

54/5510, 49/5912

0/5510

1/5510, 10/5912

 

Salivary gland

0/910, 0/ 15319, 6/8420

9/910, 153/15319, 78/8420

0/910, 0/15319, 0/8420

0/910, 0/15319, 0/8420

Thymoma

0/810, 0/3414

0/810, 28/3414

0/810, 0/3414

8/810, 6/3414

Oesophageal adenocarcinoma

1/303, 11/117

27/303, 0/117

1/303, 0/117

1/303, 0/117

Ovarian serous and endometrioid

0/191, 1/2410, 2/1115

19/191, 23/2410, 9/1115

0/191, 0/2410, 0/1115

0/191, 0/2410, 0/1115

Endometrial

3/251, 0/1010

20/251, 10/1010

0/251, 0/1010

2/251, 0/1010

Cervix, squamous cell carcinoma

0/1510

13/1510

0/1510

2/1510

Predominantly CK7-/CK20+

 

CK7+/CK20+

CK7+/CK20-

CK7-/CK20+

CK7-/CK20-

Appendiceal adenocarcinoma

1/77, 8/2318

0/77, 0 /2318

6/77, 15 /2318

0/77, 0 /2318

Appendiceal goblet cell carcinoid

1/97, 4/67

0/97, 0/67

8/97, 2/67

0/97, 0/67

Colorectal adenocarcinoma (non-mucinous and mucinous): note that CK7 positivity may be more common in rectal carcinomas.

5/511, 16/772, 4/297, 4/308, 1/2010, 12/22516, 0/1116,  1/2417, 3/2818, 1/1224, 1/1425

0/511, 0/772, 1/297, 1/308, 0/2010, 9/22516, 0/1116, 0/2818

 

 

40/511, 59/772, 23/297, 25/308, 19/2010, 3/315, 153/22516, 10/1116, 22/2417, 23/2818, 11/1224, 11/1425

6/511, 2/772, 1/297, 0/2010, 51/22516, 1/1116, 1/2417, 2/2818, 2/1425

 

 

Merkel cell carcinoma

0/910

0/910

7/910

2/910

Predominantly CK7+/CK20+

 

CK7+/CK20+

CK7+/CK20-

CK7-/CK20+

CK7-/CK20-

Small intestinal adenocarcinoma

16/2417

8/2417

0/2417

0/2417

Ovarian mucinous

14/151, 10/1818

1/151, 8/1818

0/151, 0/1818

0/151, 0/1818

 

Endocervical adenocarcinoma

7/818

1/818

0/818

0/818

Bladder, transitional cell carcinoma

17/191, 12/264, 17/289, 6/2410

2/191, 12/264, 6/289, 15/2410

0/191, 1/289, 1/2410

0/191, 4/289, 2/2410

Cholangiocarcinoma

31/4813, 6/1410, 3/418, 5/1421

15/4813, 7/1410, 0/418, 9/1421

2/4813, 0/1410, 1/418

0/4813, 1/1410, 0/418

Pancreatic adenocarcinoma

15/231, 8/1310, 11/1418

6/231, 4/1310, 3/1418

2/231, 0/1310, 0/1418

0/231, 1/1310, 0/1418

Predominantly CK7-/CK20-

 

CK7+/CK20+

CK7+/CK20-

CK7-/CK20+

CK7-/CK20-

Head and neck, squamous cell carcinoma

0/3010

8/3010

2/3010

20/3010

Lung, squamous cell

0/121, 0/1510

0/121, 7/1510, 7/823

1/121, 0/1510

11/121, 8/1510, 1/823

Lung, small cell

0/111, 0/710

2/111, 3/710, 4/523

0/111, 0/710

9/111, 4/710, 1/523

Lung, carcinoid

0/910, 0/1611

2/910, 9/1611

0/910, 0/1611

7/910, 7/1611

Oesophagus, squamous cell carcinoma

0/1410

3/1410

0/1410

11/1410

Gastrointestinal carcinoid

0/1510

2/1510

1/1510

12/1510

Colonic high grade neuroendocrine carcinoma

0/57

0/57

0/57

5/57

Hepatocellular carcinoma

2/301, 0/1110

5/301, 1/1110

0/301, 1/1110

23/301, 9/1110

Renal cell carcinoma

0/171, 0/1910

4/171, 2/1910

1/171, 0/1910

12/171, 17/1910

Prostatic adenocarcinoma

1/131, 1/599, 0/1810

1/131, 5/599, 0/1810

3/131, 5/599, 0/1810

8/131, 48/599, 18/1810

Germ cell tumour

0/1410

1/1410

0/1410

13/1410

Epithelioid sarcoma

0/1210

0/1210

0/1210

12/1210

Adrenal cortical tumour

0/1010

0/1010

0/1010

10/1010

Variable

 

CK7+/CK20+

CK7+/CK20-

CK7-/CK20+

CK7-/CK20-

Gastric adenocarcinoma

11/291, 5/143, 27/387, 1/810, 75/28916, 16/4316, 4/518

5/291, 3/143, 8/387, 2/810, 132/28916, 18/4316, 0/518

 

10/291, 3/143, 3/387, 3/810, 42/28916, 8/4316, 1/518

 

3/291, 3/143, 0/387, 2/810, 40/28916, 1/4316, 0/518

 

One must note that the cut-off percentage of staining for a positive result is varies in different studies from 1%1 to 5%10, which in part may contribute to differences in the results in some groups of carcinomas between studies. In addition, the CK 20 monoclonal antibody that was used varied (American Research Products [APR], Inc., Belmont, MA10, DAKO1).

Neither CK7 nor CK20 alone reliably differentiated pulmonary from colonic carcinomas: however, the combination is reliable, with tumours that are CK7+/CK20+ or CK7-/CK20- being of indeterminate origin. If an adenocarcinoma within the lung is being examined, TTF-1 will also be informative in combination with these cytokeratins.

Only one paper has analysed the effect of the grade on expression: aberrant cytokeratin expression is more common in poorly differentiated adenocarcinomas7.

References

1 Coordinate expression of cytokeratins 7 and 20 defines unique subsets of carcinomas. NP Wang et al. Applied Immunohistochemistry 1995; 3:99-107.

2 Loy TS, Calaluce RD. Utility of cytokeratin immunostaining in separating pulmonary adenocarcinomas from colonic carcinomas. Am J Clin Pathol 1994;102:764-767.

3 Ormsby AH et al. The utility of cytokeratin subsets in distinguishing Barrett's-related oesophageal adenocarcinoma form gastric adenocarcinoma. Histopathology 2001;38:307-311.

4 Jiang, J., Ulbright, T. M., Younger, C., Sanchez, K., Bostwick, D. G., Koch, M. O., Eble, J. N., Cheng, L. Cytokeratin 7 and cytokeratin 20 in primary urinary bladder carcinoma and matched lymph node metastasis, Arch Pathol Lab Med 2001;125:921-3.

5 Amin, M. B., Tamboli, P., Merchant, S. H., Ordonez, N. G., Ro, J., Ayala, A. G., Ro, J. Y. Micropapillary component in lung adenocarcinoma: a distinctive histologic feature with possible prognostic significance. Am J Surg Pathol 2002;26:358-364.

6 Merchant, S.H., Amin, M.B, Tamboli, P., Ro, J., Ordonez, N.G., Ayala, A.G., Czerniak, B.A. and Ro, J.Y. Primary signet-ring cell carcinoma of lung: immunohistochemical study and comparison with non-pulmonary signet-ring cell carcinomas. Am J Surg Pathol 2001;25:1515-9.

7 Kende, A.I., Carr, N.J. and Sobin, L.H. Expression of cytokeratins 7 and 20 in carcinomas of the gastrointestinal tract. Histopathology 2003;42:137-40.

8 Barbareschi, M., Murer, B., Colby, T.V., Chilosi, M., Macri, E., Loda, M. and Doglioni, C. CDX-2 Homeobox Gene Expression Is a Reliable Marker of Colorectal Adenocarcinoma Metastases to the Lungs. Am J Surg Pathol 2003;27:141-9.

9 Bassily, N.H., Vallorosi, C.J., Akdas, G., Montie, J.E. and Rubin, M.A. Coordinate expression of cytokeratins 7 and 20 in prostate adenocarcinoma and bladder urothelial carcinoma. Am J Clin Pathol 2000;113:383-8.

10 Chu, P., Wu, E., Weiss, L. M. Cytokeratin 7 and cytokeratin 20 expression in epithelial neoplasms: a survey of 435 cases. Mod Pathol 2000;13:962-972

11 Cai, Y. C., Banner, B., Glickman, J., Odze, R. D. Cytokeratin 7 and 20 and thyroid transcription factor 1 can help distinguish pulmonary from gastrointestinal carcinoid and pancreatic endocrine tumors. Human Pathol 2001;32:1087-1093

12 Bejarano, P. A., Y. E. Nikiforov, et al. (2000). "Thyroid transcription factor-1, thyroglobulin, cytokeratin 7, and cytokeratin 20 in thyroid neoplasms." Appl Immunohistochem Mol Morphol 8(3): 189-94.

13 Rullier, A., Le Bail, B., Fawaz, R., Blanc, J. F., Saric, J., Bioulac-Sage, P. Cytokeratin 7 and 20 expression in cholangiocarcinomas varies along the biliary tract but still differs from that in colorectal carcinoma metastasis. Am J Surg Pathol 200; 24:870-6.

14 Kuo, T. (2000). "Cytokeratin profiles of the thymus and thymomas: histogenetic correlations and proposal for a histological classification of thymomas." Histopathology 36(5): 403-14.

15 Jimenez-Linan M et al. Cytokeratin immunostaining differentiates endometrioid carcinoma of ovary from metastatic colorectal carcinoma. Pathological Society July 2004, abstract 78.

16 Park, S. Y., H. S. Kim, et al. (2002). "Expression of cytokeratins 7 and 20 in primary carcinomas of the stomach and colorectum and their value in the differential diagnosis of metastatic carcinomas to the ovary." Hum Pathol 33(11): 1078-85.

17 Chen, Z. M. and H. L. Wang (2004). "Alteration of cytokeratin 7 and cytokeratin 20 expression profile is uniquely associated with tumorigenesis of primary adenocarcinoma of the small intestine." Am J Surg Pathol 28(10): 1352-9.

18 Vang R, Gown AM, Barry TS, et al. Cytokeratins 7 and 20 in Primary and Secondary Mucinous Tumors of the Ovary: Analysis of Coordinate Immunohistochemical Expression Profiles and Staining Distribution in 179 Cases. Am J Surg Pathol 2006; 30:1130-1139

19 Meer S,Altini M. CK7+/CK20- immunoexpression profile is typical of salivary gland neoplasia. Histopathology 2007; 51:26-32

20 Nikitakis NG, Tosios KI, Papanikolaou VS, et al. Immunohistochemical expression of cytokeratins 7 and 20 in malignant salivary gland tumors. Mod Pathol 2004; 17:407-15 FULL TEXT

21 Khunamornpong S, Siriaunkgul S, Suprasert P, Pojchamarnwiputh S, Na Chiangmai W, Young RH. Intrahepatic cholangiocarcinoma metastatic to the ovary: a report of 16 cases of an underemphasized form of secondary tumor in the ovary that may mimic primary neoplasia. Am J Surg Pathol. 2007 Dec;31(12):1788-99.

22 Harlamert HA, Mira J, Bejarano PA, et al. Thyroid transcription factor-1 and cytokeratins 7 and 20 in pulmonary and breast carcinoma. Acta Cytol 1998; 42:1382-8

23 Chhieng DC, Cangiarella JF, Zakowski MF, et al. Use of thyroid transcription factor 1, PE-10, and cytokeratins 7 and 20 in discriminating between primary lung carcinomas and metastatic lesions in fine-needle aspiration biopsy specimens. Cancer 2001; 93:330-6 FULL TEXT

24 Zou SM, Lin DM, Lu N, et al. [Use of thyroid transcription factor-1, surfacfant protein-B, cytokeratin 7 and cytokeratin 20 in discrimination between primary and metastatic adenocarcinoma of lung]. Zhonghua Yi Xue Za Zhi 2003; 83:1350-2

25 Su YC, Hsu YC,Chai CY Role of TTF-1, CK20, and CK7 immunohistochemistry for diagnosis of primary and secondary lung adenocarcinoma. Kaohsiung J Med Sci 2006; 22:14-9 FULL TEXT

 

This page last revised 17.11.2008.

 

©SMUHT/PW Bishop