HBME-1
This antibody reacts with an antigen present in the membrane of mesothelial cells, having been raised against mesothelioma cell line SPC111. The target epitope is located in microvilli.
Immunohistochemical expression
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normal thyroid
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negative
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nodular goitre
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0/10 positive
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follicular adenoma
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3/253 positive
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oxyphilic cell adenoma
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follicular carcinoma
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19/36 positive
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papillary carcinoma
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positive
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Diagnostic utility
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adenocarcinoma
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mesothelioma
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Miettinen 199524
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174/280
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25/29
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Renshaw 1995
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17/20(pulmonary adenocarcinomas)
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20/20
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Attanoos 19965
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23/32(pulmonary adenocarcinomas)
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26/42(27 pleural and 15 peritoneal mesotheliomas)
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Savera 1996
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77/140(various sites of origin)
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19/21
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Ascoli 19976
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24%(Positivity was seen in 83% of ovarian carcinomas and 14% on non-ovarian carcinomas.)
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100%
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Bateman 19977
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10/14(primary and secondary adenocarcinomas within lung and pleura)
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17/17
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Dejmek 19978
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11/43
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78/110
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Donna 19979
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6/42
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71/84(HBME-1 was shown in 63 of 66 epithelial MM and in the epithelial component of all 8 mixed MM, with a prevailingly membranous pattern, usually homogeneous and strong, whereas none of the 10 sarcomatous MM was positive.)
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Kennedy 199710
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27/63(11/23 cases of carcinoma metastatic in pleura, 10/10 primary serous ovarian carcinomas, 3/10 primary mucinous ovarian carcinomas, and 4/20 primary renal carcinomas. )
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53/57(All cases were pleural mesotheliomas: 47 epithelioid, 7 sarcomatoid, 3 biphasic.)
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Ordonez 199711
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14/22(Cases were peripheral pulmonary adenocarcinomas involving the pleura.)
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16/20
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Riera 199712
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83/211(adenocarcinomas of various origins)
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45/57(cases were epithelial mesotheliomas.)
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Wilson 199725
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5/9(adenocarcinomas of various origins)
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12/21
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Chenard-Neu 199813
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9/30(adenocarcinomas of various origins)
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25/28
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Fetsch 1998 (on cytological specimens)14
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28/43(This study was of malignant effusions. positivity was seen in 9/15 breast, 6/7 ovarian, 2/4 prostatic, 8/8 lung and 3/9 gastrointestinal adenocarcinomas.)
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34/38(This study was of malignant effusions. )
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Ordonez 199815
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40/45(30 ovarian (10 primary and 20 metastatic to the peritoneum) and 15 primary papillary serous carcinomas of the peritoneum)
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31/35(all epithelial peritoneal mesotheliomas)
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Oates 200016
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20/42(pulmonary adenocarcinomas; 20 positive, 12 equivocal)
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20/40(20 positive, 9 equivocal)
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Brockstedt 20004
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20/57(adenocarcinomas of various origins)
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91/119
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Kayser 200117
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24/146(17/82 lung, 3/47 breast, 0/3 colon, 1/2 kidney, 3/12 site not known)
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101/118(87/99 epithelioid, 10/12 mixed and 4/7 sarcomatoid)
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Harper 200118
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10/18
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74/112
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Gonzalez-Lois 200119
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2/23(adenocarcinomas of various origins)
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40/44(33/35 epithelioid, 6/7 sarcomatoid, 0/1 mixed and 1/1 lymphohistiocytoid mesotheliomas)
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Comin 200120
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23/23(pulmonary adenocarcinomas)
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41/42
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Roberts 200126
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10/18(adenocarcinomas of various origins)
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75/112(all histological types)
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Miettinen 200128
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not studied
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20/30(20/23 epithelioid, 0/7 sarcomatoid)
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Ordonez 200327
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34/50(all primary lung adenocarcinomas: 16 case >75% of cells stained, 9 cases 50-75% of cells, 5 cases 25-50% of cells and 4 cases 1-25% of cells.)
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51/60(all epithelioid mesotheliomas: all positive cases showed thick membranous staining; 18 also showed cytoplasmic positivity. In 28 cases >75% of cells stained, in 11 cases 50-75% of cells stained,in 7 cases 25-50% of cells stained and in 5 cases 1-25% of cells stained,0, 5, 7, 11, 28)
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Overall
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49% (667/1371)
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78% (985/1256)
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A systematic review of fourteen studies (consisting of 769 epithelioid mesotheliomas and 676 pulmonary adenocarcinomas) reported sensitivities and specificities of HBME-1 for epithelioid mesothelioma of 85% and 43%29.
The staining pattern is said to be different in mesotheliomas (which have a thick, "bushy", membrane pattern) from adenocarcinomas (which have a thin membrane or a cytoplasmic staining pattern)14,20. Others5,10 consider that the patterns are not distinct and that the antibody is of little value in the differential diagnosis21. Staining is reportedly stronger in post mortem specimens that in the corresponding ante mortem specimens22.
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Positivity highlights small foci of carcinoma within benign thyroid tissue3. Positive staining for HBME-1 on a thyroid FNA is supportative evidence that the lesion is a carcinoma: a negative result does not preclude carcinoma2. HBME-1 shuld be used in a panel with other markers such as Galectin-3, CK19 and CITED1.
References
1 Miettinen, M., Karkkainen, P. Differential reactivity of HBME-1 and CD15 antibodies in benign and malignant thyroid tumours. Preferential reactivity with malignant tumours. Virchows Arch 1996;429:213-9.
2 Sack, M. J., Astengo-Osuna, C., , Lin, B. T., Battifora, H., LiVolsi, V. A. HBME-1 immunostaining in thyroid fine-needle aspirations: a useful marker in the diagnosis of carcinoma. Mod Pathol 1997;10:668-74.
3 Battifora H, HBME-1 in thyroid neoplasms in Immunohistochemistry Long Course, Nice, October 18-23, 1998.
4 Brockstedt U, Gulyas M, Dobra K. An optimized batter of eight antibodies that can distingusih most cases of epithelial mesothelioma form adenocarcinoma. Am J Clin Pathol 2000;114:203-9.
5 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.
6 Ascoli, V., Carnovale-Scalzo, C., Taccogna, S., Nardi, F. Utility of HBME-1 immunostaining in serous effusions. Cytopathology 1997;8:328-35.
7 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.
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 Donna, A., Betta, P. G., Chiodera, P. et al. Newly marketed tissue markers for malignant mesothelioma: immunoreactivity of rabbit AMAD-2 antiserum compared with monoclonal antibody HBME-1. Hum Pathol 1997;28:929-37.
10 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.
11 Ordonez, N. G.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. Am J Surg Pathol 1997;21:1399-408.
12 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.
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]. an 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 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.
16 Oates, J., Edwards, C., HBME-1, MOC-31, WT1 and calretinin: an assessment of recently described markers for mesothelioma and adenocarcinoma. Histopathology 2000;36:341-7.
17 K Kayser et al. Glyco- and immunohistochemical refinement of the differential diagnosis between mesothelioma and metastatic carcinoma and survival analysis of patients. J Pathol 2001;193:175-180.
18 Harper CM. Evaluation of a commercially available immunohistochemical diagnostic panel for malignant mesothelioma. J Pathol 2001:193(suppl):39A.
19 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.
20 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.
21 Ordonez, N. G. The immunohistochemical diagnosis of epithelial mesothelioma. Human Pathol 1999;30:313-323.
22 Roberts, F., McCall, A. E., Burnett, R. A. Malignant mesothelioma: a comparison of biopsy and postmortem material by light microscopy and immunohistochemistry. J Clin Pathol 2001;54:766-70.
23 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.
24 Miettinen M, Kovatich AJ. HBME-1: a monoclonal antibody usful in the differential diagnosis of mesothelioma,k adenocarcinoma and soft tissue and bone tumors. Appl Immunohistochem 1995;3:115-122.
25 Wilson JD, Merino MJ, Harris C et al. Mesothelioma vs adenocarcinoma; does immunohistochemistry help? Lab Invest 1997;76:174A.
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.
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 1.12.2006.
©SMUHT/PW Bishop