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

mesothelioma

carcinoma
chordoma
follicular and papillary carcinoma of thyroid, but not nodular goitre or nodular hyperplasia^1,3:

normal thyroid

negative

nodular goitre

0/10 positive

follicular adenoma

3/25³ positive

oxyphilic cell adenoma

7/46 positive

follicular carcinoma

19/36 positive

papillary carcinoma

80/90 positive

Diagnostic utility

HBME-1 is of low specificity in the differentiation of mesotheliomas from adenocarcinomas:

adenocarcinoma

mesothelioma

Miettinen 1995²⁴

174/280

25/29

Renshaw 1995

17/20 (pulmonary adenocarcinomas)

20/20

Attanoos 1996⁵

23/32 (pulmonary adenocarcinomas)

26/42 (27 pleural and 15 peritoneal mesotheliomas)

Savera 1996

77/140 (various sites of origin)

19/21

Ascoli 1997⁶

24% (Positivity was seen in 83% of ovarian carcinomas and 14% on non-ovarian carcinomas.)

100%

Bateman 1997⁷

10/14 (primary and secondary adenocarcinomas within lung and pleura)

17/17

Dejmek 1997⁸

11/43

78/110

Donna 1997⁹

6/42

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.)

Kennedy 1997¹⁰

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. )

53/57 (All cases were pleural mesotheliomas: 47 epithelioid, 7 sarcomatoid, 3 biphasic.)

Ordonez 1997¹¹

14/22 (Cases were peripheral pulmonary adenocarcinomas involving the pleura.)

16/20

Riera 1997¹²

83/211 (adenocarcinomas of various origins)

45/57 (cases were epithelial mesotheliomas.)

Wilson 1997²⁵

5/9 (adenocarcinomas of various origins)

12/21

Chenard-Neu 1998¹³

9/30 (adenocarcinomas of various origins)

25/28

Fetsch 1998 (on cytological specimens)¹⁴

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.)

34/38 (This study was of malignant effusions. )

Ordonez 1998¹⁵

40/45 (30 ovarian (10 primary and 20 metastatic to the peritoneum) and 15 primary papillary serous carcinomas of the peritoneum)

31/35 (all epithelial peritoneal mesotheliomas)

Oates 2000¹⁶

20/42 (pulmonary adenocarcinomas; 20 positive, 12 equivocal)

20/40 (20 positive, 9 equivocal)

Brockstedt 2000⁴

20/57 (adenocarcinomas of various origins)

91/119

Kayser 2001¹⁷

24/146 (17/82 lung, 3/47 breast, 0/3 colon, 1/2 kidney, 3/12 site not known)

101/118 (87/99 epithelioid, 10/12 mixed and 4/7 sarcomatoid)

Harper 2001¹⁸

10/18

74/112

Gonzalez-Lois 2001¹⁹

2/23 (adenocarcinomas of various origins)

40/44 (33/35 epithelioid, 6/7 sarcomatoid, 0/1 mixed and 1/1 lymphohistiocytoid mesotheliomas)

Comin 2001²⁰

23/23 (pulmonary adenocarcinomas)

41/42

Roberts 2001²⁶

10/18 (adenocarcinomas of various origins)

75/112 (all histological types)

Miettinen 2001²⁸

not studied

20/30 (20/23 epithelioid, 0/7 sarcomatoid)

Ordonez 2003²⁷

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.)

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)

Overall

49% (667/1371)

78% (985/1256)

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. Others^5,10 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.

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.

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.

³Battifora 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):39^A.

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.

²⁹King 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.

normal thyroid	negative
nodular goitre	0/10 positive
follicular adenoma	3/25³ positive
oxyphilic cell adenoma	7/46 positive
follicular carcinoma	19/36 positive
papillary carcinoma	80/90 positive

	adenocarcinoma	mesothelioma
Miettinen 1995²⁴	174/280	25/29
Renshaw 1995	17/20 (pulmonary adenocarcinomas)	20/20
Attanoos 1996⁵	23/32 (pulmonary adenocarcinomas)	26/42 (27 pleural and 15 peritoneal mesotheliomas)
Savera 1996	77/140 (various sites of origin)	19/21
Ascoli 1997⁶	24% (Positivity was seen in 83% of ovarian carcinomas and 14% on non-ovarian carcinomas.)	100%
Bateman 1997⁷	10/14 (primary and secondary adenocarcinomas within lung and pleura)	17/17
Dejmek 1997⁸	11/43	78/110
Donna 1997⁹	6/42	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.)
Kennedy 1997¹⁰	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. )	53/57 (All cases were pleural mesotheliomas: 47 epithelioid, 7 sarcomatoid, 3 biphasic.)
Ordonez 1997¹¹	14/22 (Cases were peripheral pulmonary adenocarcinomas involving the pleura.)	16/20
Riera 1997¹²	83/211 (adenocarcinomas of various origins)	45/57 (cases were epithelial mesotheliomas.)
Wilson 1997²⁵	5/9 (adenocarcinomas of various origins)	12/21
Chenard-Neu 1998¹³	9/30 (adenocarcinomas of various origins)	25/28
Fetsch 1998 (on cytological specimens)¹⁴	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.)	34/38 (This study was of malignant effusions. )
Ordonez 1998¹⁵	40/45 (30 ovarian (10 primary and 20 metastatic to the peritoneum) and 15 primary papillary serous carcinomas of the peritoneum)	31/35 (all epithelial peritoneal mesotheliomas)
Oates 2000¹⁶	20/42 (pulmonary adenocarcinomas; 20 positive, 12 equivocal)	20/40 (20 positive, 9 equivocal)
Brockstedt 2000⁴	20/57 (adenocarcinomas of various origins)	91/119
Kayser 2001¹⁷	24/146 (17/82 lung, 3/47 breast, 0/3 colon, 1/2 kidney, 3/12 site not known)	101/118 (87/99 epithelioid, 10/12 mixed and 4/7 sarcomatoid)
Harper 2001¹⁸	10/18	74/112
Gonzalez-Lois 2001¹⁹	2/23 (adenocarcinomas of various origins)	40/44 (33/35 epithelioid, 6/7 sarcomatoid, 0/1 mixed and 1/1 lymphohistiocytoid mesotheliomas)
Comin 2001²⁰	23/23 (pulmonary adenocarcinomas)	41/42
Roberts 2001²⁶	10/18 (adenocarcinomas of various origins)	75/112 (all histological types)
Miettinen 2001²⁸	not studied	20/30 (20/23 epithelioid, 0/7 sarcomatoid)
Ordonez 2003²⁷	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.)	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)
Overall	49% (667/1371)	78% (985/1256)