B72.3 (BRST-3)

Immunohistochemical expression

B72.3 is a monoclonal antibody directed against a high molecular weight glycoprotein known as tumour-associated glycoprotein-72 (TAG-72).   The antigen is expressed in a limited range of benign tissue but a wide range of adenocarcinomas.

Diagnostic utility

The antigen is usually expressed by adenocarcinomas, but is usually negative in mesotheliomas.

	adenocarcinoma	mesothelioma
Lafebvre 19851	17/20 (pulmonary adenocarcinomas)	2/10
Szpak 19862	21/22 (pulmonary adenocarcinomas: 19 cases showed staining of 10% or more of tumour cells)	9/19 (Eight cases showed staining of 1% of cells and one case showed staining of 5% of cells.)
Warnock 19889	43/43 (pulmonary adenocarcinomas)	3/38
Ordonez 19893	19/23 (pulmonary adenocarcinomas)	1/19
Tickman 199010 (study on cell blocks from serous fluid)	45/69 (23 mammary, 16 ovarian, 10 pulmonary, 7 gastrointestinal and 13 others)	0/2
Wick 199011	43/52 (peripheral pulmonary adenocarcinomas with pleural invasion)	0/51 (all epithelioid mesotheliomas)
Wick4	38/43 (19/23 peripheral pulmonary adenocarcinomas involving pleura, 10/10 serous surface papillary adenocarcinomas of peritoneum, 9/10 breast carcinomas metastatic to pleura. staining was predominantly membranous)	0/41 (0/21 malignant epithelioid pleural mesotheliomas, 0/20 malignant epithelioid peritoneal mesotheliomas )
McCaughey 199112	not studied	0/13
Nance 199113 (study on cell blocks from serous fluid)	15/26 (adenocarcinomas of various sites)	0/1
Wirth 199114	15/20 (pulmonary adenocarcinomas)	24/50
Gaffey 199215	not studied	1/49 (1/32 epithelioid and 0/17 biphasic)
Brown 199316	93/103 (pulmonary adenocarcinomas)	0/34 (all epithelioid mesotheliomas)
Moch 199317	22/24 (pulmonary adenocarcinomas)	9/27 (all histological types)
Dejmek 199418	15/20 (adenocarcinomas of various sites, metastatic to pleura)	13/55
Bailey 199619 (study on cell blocks from serous fluid)	10/11 (adenocarcinomas of various sites)	0/5
Delahaya 199720 (study on cell blocks from serous fluid)	68/88 (adenocarcinomas of various sites)	1/41
Riera 199721	170/211 (adenocarcinomas of various sites: 143 cases showed strong, 19 moderate and 8 weak staining. In 41 cases there was staining of >50% of cells, in 65 cases staining of 26-50% of cells and in 64 cases staining of 10-25% of cells. Staining of <10% of cells was considered as negative. Staining was generally intense but focal. A finely granular cytoplasmic staining with apical intensification was typical. Omission of heat-induced antigen retrieval decreased the number of positive adenocarcinomas without significantly increasing specificity )	2/57 (all epithelioid mesotheliomas: both positive cases showed strong staining, in one case of >50% of cells, in one case of 10-25% of cells)
Wilson 199722	8/9 (pulmonary and ovarian carcinomas)	1/21
Ordonez 199723	89/110 (pulmonary adenocarcinomas: in approximately half the cases, the staining was of >50% of the cells. The pattern of staining was coarse and granular throughout the cytoplasm, with apical accentuation.)	3/175 (in the three cases, staining was of <5% of the tumour cells)
Ordonez 199824	39/45 (30 ovarian [10 primary and 20 metastatic to the peritoneum] and 15 papillary serous carcinomas of the peritoneum)	0/35 (all epithelioid peritoneal mesotheliomas)
Leers19988	17/21 (14 cases showing staining of >10% of cells, 3 cases showed staining of <10% of cells.)	0/20
Garcia-Prats 19987	10/18 (adenocarcinomas metastatic to pleura, 10/15 pulmonary and 0/3 extra-pulmonary primaries)	0/40 (26 epithelioid, 10 sarcomatoid, 4 biphasic)
Gonzalez-Lois 20015	9/12 (metastatic to pleura from various sites)	4/44 (3/28 epithelioid, 0/5 sarcomatoid, 0/1 mixed and 1/1 lymphohistiocytoid mesotheliomas: I kno wit does not add up!)
Comin 20016	8/23 (Staining was of up to 50% of cells.)	6/42 (Staining was of up to 50% of cells.)
Ordonez 200325	42/50 (all primary lung adenocarcinomas: 8 case >75% of cells stained, 15 cases 50-75% of cells, 12 cases 25-50% of cells and 7 cases 1-25% of cells. Staining was course and granular throughout the cytoplasm.)	0/60 (all epithelioid mesotheliomas)
Overall	81% (856/1063)	8% (79/949)

A systematic review of sixteen studies (consisting of 769 pulmonary adenocarcinomas and 700 epithelioid mesotheliomas) reported sensitivities and specificities of B72.3 for pulmonary adenocarcinoma of 80% and 93%²⁶.

It may also be useful in the differentiation of non-small cell carcinomas from small cell carcinomas of the lung.

References

¹ Lafebvre MP, Rodriquez F, Schlom J et al. The application of a monoclonal antiboy in the differentiation of benign and malignant mesothelial proliferaitons from adenocarcinomas. Lab Invest 1985;52:38A (abstract)

² Szpak, C. A., Johnston, W. W., Roggli, V., Kolbeck, J., Lottich, S. C., Vollmer, R., Thor, A., Schlom, J. The diagnostic distinction between malignant mesothelioma of the pleura and adenocarcinoma of the lung as defined by a monoclonal antibody (B72.3). Am J Pathol 1986;122:252-260

³ Ordonez, N. G. The immunohistochemical diagnosis of mesothelioma. Differentiation of mesothelioma and lung adenocarcinoma. Am J Surg Pathol 1989;13:276-291.

⁴ Wick MR, Mills SE,Swanson PE Expression of "myelomonocytic" antigens in mesotheliomas and adenocarcinomas involving the serosal surfaces. Am J Clin Pathol 1990; 94:18-26

⁵ 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.

⁶ 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.

⁷ Garcia-Prats, M. D., Ballestin, C., Sotelo, T., Lopez-Encuentra, A., Mayordomo, J. I. A comparative evaluation of immunohistochemical markers for the differential diagnosis of malignant pleural tumours. Histopathology 1998;32:462-472.

⁸ 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.

⁹ Warnock, M. L., A. Stoloff, et al. (1988). "Differentiation of adenocarcinoma of the lung from mesothelioma. Periodic acid-Schiff, monoclonal antibodies B72.3, and Leu M1." Am J Pathol 133(1): 30-8.

¹⁰ Tickman, R. J., C. Cohen, et al. (1990). "Distinction between carcinoma cells and mesothelial cells in serous effusions. Usefulness of immunohistochemistry." Acta Cytol 34(4): 491-6.

¹¹ Wick, M. R., T. Loy, et al. (1990). "Malignant epithelioid pleural mesothelioma versus peripheral pulmonary adenocarcinoma: a histochemical, ultrastructural, and immunohistologic study of 103 cases." Hum Pathol 21(7): 759-66.

¹² McCaughey, W. T., T. V. Colby, et al. (1991). "Diagnosis of diffuse malignant mesothelioma: experience of a US/Canadian Mesothelioma Panel." Mod Pathol 4(3): 342-53.

¹³ Nance, K. V. and J. F. Silverman (1991). "Immunocytochemical panel for the identification of malignant cells in serous effusions." Am J Clin Pathol 95(6): 867-74.

¹⁴ Wirth, P. R., J. Legier, et al. (1991). "Immunohistochemical evaluation of seven monoclonal antibodies for differentiation of pleural mesothelioma from lung adenocarcinoma." Cancer 67(3): 655-62.

¹⁵ Gaffey, M. J., S. E. Mills, et al. (1992). "Immunoreactivity for BER-EP4 in adenocarcinomas, adenomatoid tumors, and malignant mesotheliomas." Am J Surg Pathol 16(6): 593-9.

¹⁶ Brown, R. W., G. M. Clark, et al. (1993). "Multiple-marker immunohistochemical phenotypes distinguishing malignant pleural mesothelioma from pulmonary adenocarcinoma [see comments]." Hum Pathol 24(4): 347-54.

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 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.

²⁰ 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.

²¹ Riera, J. R., C. Astengo-Osuna, et al. (1997). "The immunohistochemical diagnostic panel for epithelial mesothelioma: a reevaluation after heat-induced epitope retrieval [see comments]." Am J Surg Pathol 21(12): 1409-19.

²² Wilson JD, Merino MJ, Harris C et al. Mesothelioma vs adenocarcinoma: does immunohistochemistry help? Lab Invest 1997;76:174A.

²³ 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.

²⁴ Ordonez, N. G. (1998). "Role of immunohistochemistry in distinguishing epithelial peritoneal mesotheliomas from peritoneal and ovarian serous carcinomas." Am J Surg Pathol 22(10): 1203-14.

²⁵ 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.

²⁶ 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