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.
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adenocarcinoma
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mesothelioma
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Lafebvre 19851
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17/20(pulmonary adenocarcinomas)
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2/10
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Szpak 19862
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21/22(pulmonary adenocarcinomas: 19 cases showed staining of 10% or more of tumour cells)
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9
/19(Eight cases showed staining of 1% of cells and one case showed staining of 5% of cells.)
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Warnock 19889
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43/43(pulmonary adenocarcinomas)
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3/38
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Ordonez 19893
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19/23(pulmonary adenocarcinomas)
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1/19
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Tickman 199010 (study on cell blocks from serous fluid)
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45/69(23 mammary, 16 ovarian, 10 pulmonary, 7 gastrointestinal and 13 others)
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0/2
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Wick 199011
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43/52(peripheral pulmonary adenocarcinomas with pleural invasion)
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0/51(all epithelioid mesotheliomas)
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Wick4
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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)
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0/41(0/21 malignant epithelioid pleural mesotheliomas, 0/20 malignant epithelioid peritoneal mesotheliomas )
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McCaughey 199112
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not studied
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0/13
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Nance 199113 (study on cell blocks from serous fluid)
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15/26(adenocarcinomas of various sites)
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0/1
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Wirth 199114
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15/20(pulmonary adenocarcinomas)
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24/50
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Gaffey 199215
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not studied
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1/49(1/32 epithelioid and 0/17 biphasic)
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Brown 199316
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93/103(pulmonary adenocarcinomas)
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0/34(all epithelioid mesotheliomas)
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Moch 199317
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22/24(pulmonary adenocarcinomas)
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9/27(all histological types)
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Dejmek 199418
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15/20(adenocarcinomas of various sites, metastatic to pleura)
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13/55
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Bailey 199619 (study on cell blocks from serous fluid)
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10/11(adenocarcinomas of various sites)
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0/5
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Delahaya 199720 (study on cell blocks from serous fluid)
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68/88(adenocarcinomas of various sites)
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1/41
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Riera 199721
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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 )
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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)
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Wilson 199722
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8/9(pulmonary and ovarian carcinomas)
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1/21
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Ordonez 199723
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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.)
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3/175(in the three cases, staining was of <5% of the tumour cells)
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Ordonez 199824
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39/45(30 ovarian [10 primary and 20 metastatic to the peritoneum] and 15 papillary serous carcinomas of the peritoneum)
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0/35(all epithelioid peritoneal mesotheliomas)
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Leers19988
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17/21(14 cases showing staining of >10% of cells, 3 cases showed staining of <10% of cells.)
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0/20
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Garcia-Prats 19987
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10/18(adenocarcinomas metastatic to pleura, 10/15 pulmonary and 0/3 extra-pulmonary primaries)
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0/40(26 epithelioid, 10 sarcomatoid, 4 biphasic)
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Gonzalez-Lois 20015
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9/12(metastatic to pleura from various sites)
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4/44(3/28 epithelioid, 0/5 sarcomatoid, 0/1 mixed and 1/1 lymphohistiocytoid mesotheliomas: I kno wit does not add up!)
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Comin 20016
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8/23(Staining was of up to 50% of cells.)
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6/42(Staining was of up to 50% of cells.)
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Ordonez 200325
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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.)
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0/60(all epithelioid mesotheliomas)
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Overall
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81% (856/1063)
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8% (79/949)
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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