CD15 (LeuM1)

Leu-M1 was first reported as reactive with the membrane-related trisaccharide fucosyl-N-acetyllactosamine on myelomonocytic cells, where the epitope was known as X-Hapten.

Antibodies are effective on paraffin-embedded tissue¹².

Immunohistochemical expression

Mature granulocytes; promyelocytes stain variably and normal myeloblasts are negative.

Activated lymphocytes, mainly T cells

• Leukaemic myeloid and monocytic cells. Almost all cases of CML are positive. Lower rates of positivity are seen in ALL.

• Reed-Sternberg cells and mononuclear Hodgkin's cells, staining about 80% of cases of classical Hodgkin lymphoma¹¹. The staining is characteristically membrane plus a paranuclear focus associated with the Golgi apparatus

• Granulocytic sarcoma

• Most adenocarcinoma

Diagnostic utility

• Hodgkin's disease

• Granulocytic sarcoma

• Differentiation of adenocarcinoma from mesothelioma: interpretation may be difficult in cases in which tumour cells have phagocytosed inflammatory cells, or the CD15 released by dying inflammatory cells⁶.

	adenocarcinoma	mesothelioma
Sheibani 19868	47/50	0/28
Sheibani 198614	105/179 (various sites of origin, including lung)	0/18
Warnock 198815	34/44 (pulmonary adenocarcinomas and large cell carcinomas)	2/27
Ordonez 198916	14/23 (primary pulmonary adenocarcinomas)	0/19 (all epithelioid mesotheliomas)
Wick 19909	52/52 (peripheral adenocarcinoma of the lung with pleural invasion)	0/51 (epithelioid pleural mesotheliomas)
Wick 199040	38/43 (23/23 peripheral pulmonary adenocarcinomas involving pleura, 8/10 serous surface papillary adenocarcinomas of peritoneum, 7/10 breast carcinomas metastatic to pleura. staining was predominantly membranous)	0/41 (0/21 malignant epithelioid pleural mesotheliomas, 3/20 malignant epithelioid peritoneal mesotheliomas showed reactivity of minute foci of 5-10 cells)
O'Hara 199017	23/28 (primary pulmonary adenocarcinomas)	0/20
Tickman 199018 (study done on cell blocks from serous effusions)	30/69 (23 mammary, 16 ovarian, 10 pulmonary, 7 gastrointestinal and 13 others)	0/2
McCaughey 199119	not studied	2/98
Nance 199120 (study done on cell blocks from serous effusions)	11/26 (various sites of origin)	0/1
Wirth 199121	16/20 (primary pulmonary adenocarcinomas)	4/50
Collins 199222	26/48 (primary pulmonary adenocarcinomas)	1/31 (one case showed minimal focal positivity)
Gaffey 199223	not studied	0/49 (32 epithelioid and 17 biphasic)
Brown 199324	79/103 (primary pulmonary adenocarcinomas)	2/34 (all epithelioid mesotheliomas)
Moch 199325	16/24 (primary pulmonary adenocarcinomas)	0/27 (all histological types)
Dejmek 199426	38/43 (various sites of origin)	31/93
Maquire 199427 (study done on cell blocks from serous effusions)	18/23 (primary pulmonary adenocarcinomas)	0/44
Bailey 199628 (study done on cell blocks from serous effusions)	8/11 (primary pulmonary adenocarcinomas)	0/5
Doglioni 19961	19/22	0/20
Dejmek 19975	35/43	22/110
Bateman 199729	6/14 (various sites of origin, metastatic to lung and pleura)	0/17
Delahaye 199730 (study done on cell blocks from serous effusions)	25/88 (various sites of origin)	0/41
Riera 199731	159/211 (various sites of origin: 115 cases intense, 35 moderate and 9 weak staining. 70 cases stained >50% of cells, 46 cases 26-50% of cells and 9 cases 10-25% of cells. 104/123 lung adenocarcinomas were positive. Staining of <10% of cells was considered negative.)	2/57 (all epithelioid mesotheliomas: the two cases showed intense, predominantly membrane, staining but on only 10-25% of cells. Staining of <10% of cells was considered negative.)
Wilson 199732	8/9 (lung and ovarian carcinomas)	3/21
Ordonez 199733	65/92 (primary pulmonary adenocarcinomas)	0/120
Leers 199810	9/21 (various sites of origin. All 9 cases showing staining of >10% of cells.)	2/20 (Both cases showed staining of <10% of cells.)
Chenard-Neu 199834	15/30 (various sites of origin)	0/28
Garcia-Prats 199835	8/18 (7/15 pulmonary and 1/3 extra-pulmonary adenocarcinomas, metastatic to pleura)	2/40 (1/26 epithelioid, 1/10 sarcomatoid, 0/4 biphasic)
Ordonez 199836	28/45 (30 ovarian [10 primary and 20 metastatic to the peritoneum] and 15 papillary serous carcinomas of the peritoneum)	0/35 (all epithelial peritoneal mesotheliomas)
Brockstedt 20002	46/57 (primary pulmonary adenocarcinomas)	18/119
Dejmek 200037 (cytospins of serous fluids)	24/47 (primary pulmonary adenocarcinomas)	5/35
Gonzalez-Lois 200138	8/11 (primary pulmonary adenocarcinomas)	3/41 (3/33 epithelioid, 0/6 sarcomatoid, 0/1 mixed and 0/1 lymphohistiocytoid mesotheliomas)
Roberts 20014	9/18 (various sites of origin)	7/111 (6/81 epithelioid, 0/11 sarcomatoid, 1/12 biphasic and 0/7 desmoplastic)
Comin 20017	23/23 (primary pulmonary adenocarcinomas)	2/42 (In the two cases which stained, less than 25% of cells were positive.)
Miettinen 2001	not studied	9/24 (5/17 epithelioid, 4/7 sarcomatoid: usually limited to <5% of tumour cells.)
Abutaily 200213	5/11 (pulmonary adenocarcinomas: only the 11 of 35 cases which were E-cadherin positive / TTF-1 negative were tested)	0/9
Ordonez 200339	36/50 (all primary lung adenocarcinomas: 7 case >75% of cells stained, 13 cases 50-75% of cells, 9 cases 25-50% of cells and 4 cases 1-25% of cells. Staining was granular in most cases, membranous in a minority.)	0/60 (all epithelioid mesotheliomas)
Overall	68% (1091/1606)	7% (120/1646)

A systematic review of twenty six studies (consisting of 1473 pulmonary adenocarcinomas and 1204 epithelioid mesotheliomas) reported sensitivities and specificities of CD15 for pulmonary adenocarcinoma of 72% and 93%⁴¹.

References

¹ 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 Pathol1996;20:1037-46.

² Brockstedt U, Gulyas M, Dobra K. an optimized batter of eight antibodies that can distinguish most cases of epithelial mesothelioma form adenocarcinoma. Am J Clin Pathol 2000;114:203-9.

³ 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.

⁴ 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. First published in abstract, Harper CM. Evaluation of a commercially available immunohistochemical diagnostic panel for malignant mesothelioma. J Pathol 2001:193(suppl):39^A.

⁵ 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.

⁶ Sosolik, R. C., McGaughy, V. R., De Young, B. R. Anti-MOC-31: a potential addition to the pulmonary adenocarcinoma versus mesothelioma immunohistochemistry panel. Mod Pathol 1997;10:716-9.

⁷ 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.

⁸ Sheibani, K., Battifora, H., Burke, J. S.Sheibani. Antigenic phenotype of malignant mesotheliomas and pulmonary adenocarcinomas. An immunohistologic analysis demonstrating the value of Leu M1 antigen. Am J Pathol 1986;123:212-219

⁹ Wick, M. R., Loy, T., Mills, S. E., Legier, J. F., Manivel, J. C. Malignant epithelioid pleural mesothelioma versus peripheral pulmonary adenocarcinoma: a histochemical, ultrastructural, and immunohistologic study of 103 cases. Hum Pathol 1990;21:759-766.

¹⁰ 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.

¹¹ Pileri, S. A., Ascani, S., Leoncini, L., Sabattini, E., Zinzani, P. L., Piccaluga, P. P., Pileri, A., Jr., Giunti, M., Falini, B., Bolis, G. B., Stein, H. Hodgkin's lymphoma: the pathologist's viewpoint. J Clin Pathol 2002;5:162-176.

¹²Leong A S-Y, Cooper K and Leong FJ W-M. Manual of diagnostic antibodies for immunohistology. 2nd edition, 2003

¹³ 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.

¹⁴ Sheibani, K., H. Battifora, et al. (1986). "Leu-M1 antigen in human neoplasms. An immunohistologic study of 400 cases." Am J Surg Pathol 10(4): 227-36.

¹⁵ 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.

¹⁶ Ordonez, N. G. (1989). "The immunohistochemical diagnosis of mesothelioma. Differentiation of mesothelioma and lung adenocarcinoma." Am J Surg Pathol 13(4): 276-91.

¹⁷ O'Hara, C. J., J. M. Corson, et al. (1990). "ME1. A monoclonal antibody that distinguishes epithelial-type malignant mesothelioma from pulmonary adenocarcinoma and extrapulmonary malignancies." Am J Pathol 136(2): 421-8.

¹⁸ 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.

¹⁹ 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.

²⁰ 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.

²¹ 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.

²² Collins, C. L., N. G. Ordonez, et al. (1992). "Thrombomodulin expression in malignant pleural mesothelioma and pulmonary adenocarcinoma." Am J Pathol 141(4): 827-33.

²³ 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.

²⁴ 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.

²⁵ 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.

²⁶ Dejmek, A. and A. Hjerpe (1994). "Immunohistochemical reactivity in mesothelioma and adenocarcinoma: a stepwise logistic regression analysis." Apmis 102(4): 255-64.

²⁷ 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.

²⁸ 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.

²⁹ Bateman, A. C., R. K. al-Talib, et al. (1997). "Immunohistochemical phenotype of malignant mesothelioma: predictive value of CA125 and HBME-1 expression." Histopathology 30(1): 49-56.

³⁰ 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.

³¹ 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.

³² Wilson JD, Merino MJ, Harris C et al. Mesothelioma vs adenocarcinoma: does immunohistochemistry help? Lab Invest 1997;76:174A.

³³ 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.

³⁴ Chenard-Neu, M. P., A. Kabou, et al. (1998). "[Immunohistochemistry in the differential diagnosis of mesothelioma and adenocarcinoma. Evaluation of 5 new antibodies and 6 traditional antibodies]." Ann Pathol 18(6): 460-5.

³⁵ 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.

³⁶ 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.

³⁷ 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.

³⁸ Gonzalez-Lois, C., C. Ballestin, et al. (2001). "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 38(6): 528-34.

³⁹ 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.

⁴⁰ 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

⁴¹ 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