Thrombomodulin (CD141)

This 75 kD glycoprotein converts thrombin from a procoagulant protease to an anticoagulant. It was originally thought to be useful as a vascular marker but lacks specificity for endothelium

Immunohistochemical expression

 

conclusion regarding usefulness

adenocarcinoma

mesothelioma

Fink 199220

yes

1/15

8/8

Collins 19922

yes

4/48

31/31

Brown 19933

no

62/103

20/34

Ascoli 19954

yes

44/119

33/33

Attanoos 19955

 

1/20

11/20

Attanoos 19966

yes

2/32

22/42

Doglioni 19967

no

17/22

16/20

Dejmek 19978

 

10/43

69/110 

Kennedy 19979

yes

8/63

49/57

Ordonez 199710

yes

7/46

32/42

Riera 199711

no

13/211

28/57

Ordonez 199812

yes

1/45

26/35

Chenard-Neu 199813

no

4/30

12/28

Fetsch 199814

no

21/40

24/36

Cury 200015

yes

12/63

55/61

Brockstedt 200016

yes

13/57

74/119

Roberts 200026

no

2/18

25/82

Carella 200117

yes

1/20

29/46

Harper 200118

 

2/18

32/112

Comin 200121

yes

5/23

39/42

Foster 200125

no

4/51

23/67

Miettinen 200323

 

not studied

25/28

Miettinen 200323

 

32/256

16/27

Abutaily 2002 24

 

2/35

22/41

Ordonez 200327

no

7/50

46/60

Overall

Limited

19% (273/1428)

62% (767/1238)

A systematic review of sixteen studies (consisting of 831 epithelioid mesotheliomas and 964 pulmonary adenocarcinomas) reported sensitivities and specificities of thrombomodulin for epithelioid mesothelioma of 61% and 80%29.

Staining is membranous in mesotheliomas but, in those adenocarcinomas which stain, there is additional cytoplasmic staining21. Granular cytoplasmic staining in mesothelioma may be a manifestation of absorption and may be seen in association with degneration and necrosis27.

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. Common positivity limits the value of thrombomodulin in separating carcinomas other than adenocarcinoma from mesotheliomas.

adenocarcinoma

acinar type, differentiated

19/148 23

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

7/49 23

bronchoalveolar, mucinous

1/6 23

bronchoalveolar, non-mucinous

1/7 23

acinar with focal neuroendocrine differentiation

0/22 23

neuroendocrine

3/18 23

clear cell

1/6 23

large cell

NOS

29/117 23

with focal neuroendocrine differentiation

3/10 23

neuroendocrine carcinoma

6/33 23

small cell carcinoma

11/41 23

squamous cell

keratinising

62/62 23

non-keratinising

54/62 23

NOS

33/331

sarcomatoid carcinoma, spindle cell

1/6 23

giant cell carcinoma

3/6 23

 

Most studies have been of mesothelioma versus primary pulmonary adenocarcinoma. Some metastatic carcinomas, such as renal cell carcinoma, pose particular problems.

 

Diagnostic utility

References

1 Tolnay, E., Wiethege, T., Muller, K. M. Expression and localization of thrombomodulin in preneoplastic bronchial lesions and in lung cancer. Virchows Arch 1997;430:209-12.

2 Collins, C. L., Ordonez, N., Schaefer, R. Thrombomodulin expression in malignant pleural mesothelioma and pulmonary adenocarcinoma. Am J Pathol 1992;141:827-33.

3 Brown, R. W., Clark, G. M., Tandon, A. K., Allred, D. C. Multiple-marker immunohistochemical phenotypes distinguishing malignant pleural mesothelioma from pulmonary adenocarcinoma. Hum Pathol 1993;24:347-54.

4 Ascoli, V., Scalzo, C. C., Taccogna, S., Nardi, F. The diagnostic value of thrombomodulin immunolocalization in serous effusions. Arch Pathol Lab Med 1995; 119:1136-40.

5 Attanoos, R. L., Goddard, H., Thomas, et al. A comparative immunohistochemical study of malignant mesothelioma and renal cell carcinoma: the diagnostic utility of Leu-M1, Ber EP4, Tamm- Horsfall protein and thrombomodulin. Histopathology 1995;27:361-6.

6 Attanoos, R. L., Goddard, H., Gibbs, A. R. Mesothelioma-binding antibodies: thrombomodulin, OV 632 and HBME-1 and their use in the diagnosis of malignant mesothelioma. Histopathology 1996;29:209-15.

7 Doglioni, C.,Tos, A. P.,Laurino, L.,Iuzzolino, P., Chiarelli, C., Celio, M. R., Viale, G. Calretinin: a novel immunocytochemical marker for mesothelioma. Am J Surg Pathol 1996;20:1037-46.

8 Dejmek, A., Brockstedt, U., Hjerpe, A. Optimization of a battery using nine immunocytochemical variables for distinguishing between epithelial mesothelioma and adenocarcinoma. Apmis 1997;105:889-94.

9 Kennedy, A. D., King, G., Kerr, K. M. HBME-1 and antithrombomodulin in the differential diagnosis of malignant mesothelioma of pleura. J Clin Pathol 1997;50:859-62.

10 Ordonez, N. G. Value of thrombomodulin immunostaining in the diagnosis of mesothelioma. Histopathology 1997;31:25-30.

11 Riera, J. R., Astengo-Osuna, C., Longmate, J. A. Battifora, H. The immunohistochemical diagnostic panel for epithelial mesothelioma: a reevaluation after heat-induced epitope retrieval. Am J Surg Path 1997;21:1409-19.

12 Ordonez, N. G. Role of immunohistochemistry in distinguishing epithelial peritoneal mesotheliomas from peritoneal and ovarian serous carcinomas. Am J Surg Pathol 1998;22:1203-14.

13 Chenard-Neu, M. P., Kabou, A., Mechine, A., et al. [Immunohistochemistry in the differential diagnosis of mesothelioma and adenocarcinoma. Evaluation of 5 new antibodies and 6 traditional antibodies]. Ann Pathol 1998;18:460-5.

14 Fetsch, P. A., Abati, A., Hijazi, Y. M. Utility of the antibodies CA 19-9, HBME-1, and thrombomodulin in the diagnosis of malignant mesothelioma and adenocarcinoma in cytology. Cancer 1998;84:101-8.

15 Cury, P. M., Butcher, D. N., Fisher, C. Value of the mesothelium-associated antibodies thrombomodulin, cytokeratin 5/6, calretinin, and CD44H in distinguishing epithelioid pleural mesothelioma from adenocarcinoma. Mod Pathol 2000;13:107-12.

16 Brockstedt U, Gulyas M, Dobra K. An optimized batter of eight antibodies that can distingusih most cases of epithelial mesothelioma from adenocarcinoma. Am J Clin Pathol 2000;114:203-9

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

18 Harper CM. Evaluation of a commercially available immunohistochemical diagnostic panel for malignant mesothelioma. J Pathol 2001:193(suppl):39A.

19 Nicholson, S. A., McDermott, M. B., DeYoung, B. R., Swanson, P. E. CD31 immunoreactivity in small round cell tumors. Appl Immunohistochem Molecul Morphol 2000;8:19-24.

20 Fink. Lab Invest 1992;66:113A

21 Comin, C. E., Novelli, L., Boddi, V., Paglierani, M., Dini, S. Calretinin, thrombomodulin, CEA, and CD15: a useful combination of immunohistochemical markers for differentiating pleural epithelial mesothelioma from peripheral pulmonary adenocarcinoma. Hum Pathol 2001;32:529-536.

22 Diagnostic Immunohistochemistry edited by Professor D. J. Dabbs, page 71

23 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.

24 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.

25 Foster, M. R., J. E. Johnson, et al. (2001). "Immunohistochemical analysis of nuclear versus cytoplasmic staining of WT1 in malignant mesotheliomas and primary pulmonary adenocarcinomas." Arch Pathol Lab Med 125(10): 1316-20.

26 Roberts, F., C. M. Harper, et al. (2001). "Immunohistochemical analysis still has a limited role in the diagnosis of malignant mesothelioma. A study of thirteen antibodies." Am J Clin Pathol 116(2): 253-62. (Initial publication of data as abstract 8Harper CM. Evaluation of a commercially available immunohistochemical diagnostic panel for malignant mesothelioma. J Pathol 2001:193(suppl):39A.)

27 Ordonez, N. G. (2003). "The immunohistochemical diagnosis of mesothelioma: a comparative study of epithelioid mesothelioma and lung adenocarcinoma." Am J Surg Pathol 27(8): 1031-51.

28 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.

29 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

 

This page last revised 16.2.2006.

 

©SMUHT/PW Bishop