The Ber-EP4 antibody was generated using a membrane-enriched fraction derived from the MDF-7 breast cancer cell line. It reacts with an epitope present on two glycoproteins (of 30 and 34 kD respectively)36.

Prolonged formalin fixation of more than 48 hours has been reported to lead to loss of antigenicity11, although others have not found this11.

Immunohistochemical expression

Present on all epithelial cells, except the superficial layers of squamous epithelium, hepatocytes and parietal cells.

Diagnostic utility




Latza 199011



Kuhlmann 199116 (study done on cell blocks prepared from serous fluid)



Sheibani 19921



Gaffy 199212



Moch 199317



Dejmek 199418



Grove 199419



Maguire 199420 (study done on cell blocks prepared from serous fluid)



Shield 199421 (study done on cell blocks prepared from serous fluid)



Ascoli 199522 (study done on cell blocks prepared from serous fluid)



Atanoos 199523



Doglioni 199613



Bailey 199624 (study done on cell blocks prepared from serous fluid)



Kuenen-Boumeester 199625 (study done on cell blocks prepared from serous fluid)



Bateman 19972



Dejmek 19973



Riera 19974



Delahaye 199726 (study done on cell blocks prepared from serous fluid)




Ordonez 199727



Wilson 199728



Chenard-Neu 19985



Leers 199814



Garcia-Prats 199829



Ordonez 199830



Brockstedt 20006



Dejmek 200031 (study done on cell blocks prepared from serous fluid)



Gonzalez-Lois 20017



Harper 20018



Carella 20019



Comin 200110



Davidson 200132 (study done on cell blocks prepared from serous fluid)



Miettinen 200133

not studied


Abutaily 2002 15



Ordonez 200334




80% (1394/1750)

12% (174/1445)

A systematic review of seventeen studies (consisting of 702 pulmonary adenocarcinomas and 899 epithelioid mesotheliomas) reported sensitivities and specificities of BerEP4 for pulmonary adenocarcinoma of 80% and 90%38.


1 Sheibani K, Esteban JM, Bailey A, Batifora H, Weiss I.  Immunologic and molecular studies as an aid to the diagnosis or malignant mesothelioma.  Human Pathology 1992; 23: 107-116.

2 Bateman, A. C., al-Talib, R. K., Newman, T., Williams, J. H., Herbert, A. Immunohistochemical phenotype of malignant mesothelioma: predictive value of CA125 and HBME-1 expression. Histopathology 1997;30:49-56.

3 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.

4 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.

5 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. [French]

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

7 Gonzalez-Lois, C., Ballestin, C., Sotelo, M. T., Lopez-Rios, F., Garcia-Prats, M. D., Villena, V. Combined use of novel epithelial (MOC-31) and mesothelial (HBME-1) immunohistochemical markers for optimal first line diagnostic distinction between mesothelioma and metastatic carcinoma in pleura. Histopathology 2001;38:528-34.

8 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. Initially published in abstract as Harper CM. Evaluation of a commercially available immunohistochemical diagnostic panel for malignant mesothelioma. J Pathol 2001:193(suppl):39A.

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

10 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.

11 Latza, U., Niedobitek, G., Schwarting, R., Nekarda, H., Stein, H. Ber-EP4: new monoclonal antibody which distinguishes epithelia from mesothelial. J Clin Pathol 1990;43:213-219.

12 Gaffey, M. J., Mills, S. E., Swanson, P. E., Zarbo, R. J., Shah, A. R., Wick, M. R. Immunoreactivity for BER-EP4 in adenocarcinomas, adenomatoid tumors, and malignant mesotheliomas Am J Surg Pathol 1992;16:593-599

13 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.

14 Leers, M. P., Aarts, M. M., Theunissen, P. H. E-cadherin and calretinin: a useful combination of immunochemical markers for differentiation between mesothelioma and metastatic adenocarcinoma. Histopathology 1998;32:209-216.

15 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.

16 Kuhlmann, L., K. H. Berghauser, et al. (1991). "Distinction of mesothelioma from carcinoma in pleural effusions. An immunocytochemical study on routinely processed cytoblock preparations." Pathol Res Pract 187(4): 467-71.

17 Moch, H., M. Oberholzer, et al. (1993). "Diagnostic tools for differentiating between pleural mesothelioma and lung adenocarcinoma in paraffin embedded tissue. Part I: Immunohistochemical findings." Virchows Arch A Pathol Anat Histopathol 423(1): 19-27.

18 Dejmek, A. and A. Hjerpe (1994). "Immunohistochemical reactivity in mesothelioma and adenocarcinoma: a stepwise logistic regression analysis." Apmis 102(4): 255-64.

19 Grove, A., S. M. Paulsen, et al. (1994). "The value of immunohistochemistry of pleural biopsy specimens in the differential diagnosis between malignant mesothelioma and metastatic carcinoma." Pathol Res Pract 190(11): 1044-55.

20 Maguire, B., D. Whitaker, et al. (1994). "Monoclonal antibody Ber-EP4: its use in the differential diagnosis of malignant mesothelioma and carcinoma in cell blocks of malignant effusions and FNA specimens." Diagn Cytopathol 10(2): 130-4.

21 Shield, P. W., J. J. Callan, et al. (1994). "Markers for metastatic adenocarcinoma in serous effusion specimens." Diagn Cytopathol 11(3): 237-45.

22 Ascoli, V., C. C. Scalzo, et al. (1995). "The diagnostic value of thrombomodulin immunolocalization in serous effusions." Arch Pathol Lab Med 119(12): 1136-40.

23 Attanoos, R. L., H. Goddard, et al. (1995). "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 27(4): 361-6.

24 Bailey, M. E., R. W. Brown, et al. (1996). "Ber-EP4 for differentiating adenocarcinoma from reactive and neoplastic mesothelial cells in serous effusions. Comparison with carcinoembryonic antigen, B72.3 and Leu-M1." Acta Cytol 40(6): 1212-6.

25 Kuenen-Boumeester, V., P. van Loenen, et al. (1996). "Quality control of immunocytochemical staining of effusions using a standardized method of cell processing." Acta Cytol 40(3): 475-9.

26 Delahaye, M., F. van der Ham, et al. (1997). "Complementary value of five carcinoma markers for the diagnosis of malignant mesothelioma, adenocarcinoma metastasis, and reactive mesothelium in serous effusions." Diagn Cytopathol 17(2): 115-20.

27 Ordonez, N. G. (1997). "The value of antibodies 44-3A6, SM3, HBME-1, and thrombomodulin in differentiating epithelial pleural mesothelioma from lung adenocarcinoma: a comparative study with other commonly used antibodies [see comments]." Am J Surg Pathol 21(12): 1399-408.

28 Wilson JD, Merino MJ, Harris C et al. Mesothelioma vs adenocarcinoma: does immunohistochemistry help? Lab Invest 1997;76:174A.

29 Garcia-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.

30 Ordonez, N. G. (1998). "Value of the Ber-EP4 antibody in differentiating epithelial pleural mesothelioma from adenocarcinoma. The M.D. Anderson experience and a critical review of the literature." Am J Clin Pathol 109(1): 85-9.

31 Dejmek, A. and A. Hjerpe (2000). "Reactivity of six antibodies in effusions of mesothelioma, adenocarcinoma and mesotheliosis: stepwise logistic regression analysis." Cytopathology 11(1): 8-17.

32 Davidson, B., S. Nielsen, et al. (2001). "The role of desmin and N-cadherin in effusion cytology: a comparative study using established markers of mesothelial and epithelial cells." Am J Surg Pathol 25(11): 1405-12.

33 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.

34 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.

35 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.

36 Ordonez, N. G. (1998). "Desmoplastic small round cell tumor: II: an ultrastructural and immunohistochemical study with emphasis on new immunohistochemical markers." Am J Surg Pathol 22(11): 1314-27.

37 Pan, C. C., P. C. Chen, et al. (2004). "The diagnostic utility of MOC31, BerEP4, RCC marker and CD10 in the classification of renal cell carcinoma and renal oncocytoma: an immunohistochemical analysis of 328 cases." Histopathology 45(5): 452-9.

38 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

39 Fan YS, Carr RA, Sanders DS, et al. Characteristic Ber-EP4 and EMA expression in sebaceoma is immunohistochemically distinct from basal cell carcinoma. Histopathology 2007; 51:80-6

This page last revised 12.8.2007.

©SMUHT/PW Bishop