HBME-1 (Mesothelial Cell)

Sources/Clones
Dako (HBME-1).

Fixation/Preparation
The antibody is immunoreactive in formalin-fixed, paraffin-embedded tissue sections and in frozen sections and cell preparations.

Background
The antibody reacts with an antigen present in the membrane of mesothelial cells and their neoplastic counterparts, particularly epithelioid mesotheliomas. In initial testing the antibody failed to decorate epithelial cells of the kidney, lung, liver, ovary and pancreas. The antibody was derived from human epithelioid mesothelioma cells.

Applications
The antibody was designed primarily for the identification of normal and neoplastic mesothelial cells from metastatic carcinoma and is useful in this context. However, like many previous attempts to produce a mesothelial cell-specific antibody, HBME-1 has met with limited success. In one study, HBME-1 labeled all 17 cases of mesothelioma but also adenocarcinoma cells in ten of 14 cases (Bateman et al, 1997). Among other markers employed in the same study, the authors found that CA 125 labeled 15 of 17 mesotheliomas and seven of 14 adenocarcinomas. They concluded that both HBME-1 and CA 125 were not sufficiently specific to be employed on their own as mesothelial markers but made a contribution when used in an appropriate panel. Similar results have been previously reported (Attanoos et al, 1996). Negative staining for HBME-1 makes the diagnosis of mesothelioma unlikely. A study of serous effusions revealed HBME-1 reactivity on the membranes of all reactive and malignant mesothelial cells but also in 24% of metastatic carcinomas and as many as 83% of ovarian carcinomas (Ascoli et al, 1997). HBME-1 does not label sarcomatous malignant mesothelioma (Donna et al, 1997).
HBME-1 produces a ''thick pattern of immunoreactivity of the cell surfaces, often including the intracytoplasmic lumina" and is said to show excellent correlation with the presence of abundant long microvilli with electron microscopy (Battifora & McCaughey, 1995). There is usually no cytoplasmic labeling and although adenocarcinoma cells may show membrane staining, they do not display the characteristic "thick" membranes and may show cytoplasmic staining. A similar pattern of immunoreactivity with antiepithelial membrane antigen (anti-EMA) was described earlier by Leong et al (1990) and corresponds to labeling of the cell membranes and long microvilli characteristic of mesothelioma cells (Van Der Kwast et al, 1987). It was emphasized that the microvillous processes which are visible with EMA immunostaining are not only abnormally long but their circumferential distribution around the cell is aberrant in nature and signifies malignancy (Leong & Vermin-Roberts, 1994).

Comments
As with EMA, immunostaining with HBME-1 is aimed at highlighting the cell membranes and long microvilli. Optimal dilutions of the antibody have to be ascertained before use in diagnostic panels as high concentrations will result in cytoplasmic staining of both mesothelioma and adenocarcinoma cells, reducing the usefulness of HBME-1 as a diagnostic discriminator between the two entities.

References
•Attanoos RL, Goddard H, Gibbs AR 1996. Mesothelioma-binding antibodies: thrombomodulin, OV 632 and HBME-1 and their use in the diagnosis of malignant mesothelioma. Histopathology 29: 209-215.

•Ascoli V, Carnovale-Scalzo C, Taccogna S, Nardi F 1997. Utility of HBME-1 immunostaining in serous effusions. Cytopathology 8: 328-335.

•Bateman AC, Al-Talib RK, Newman T, Williams, Herbert A 1997. Immunohistochemical phenotype of malignant mesothelioma: predictive value of CA 125 and HBME-1 expression. Histopathology 30: 49-56.

•Battifora H, McCaughey WTE 1995. Tumors of the serosal membranes. Atlas of tumor pathology, 3rd series, fascicle 15. Washington DC: Armed Forces Institute of Pathology, p 73.

•Donna A, Betta PG, Chiodera P et al 1997. Newly marketed tissue markers for malignant mesothelioma: immunoreactivity of rabbit AMAD-2 antiserum compared with monoclonal antibody HBME-1 and a review of the literature on so-called mesothelioma antibodies. Human Pathology 28:929-937.

•Leong AS-Y, Vermin-Roberts E 1994. The immunohistochemistry of malignant mesothelioma. Pathology Annual 29:157-159.

•Leong AS-Y, Parkinson R, Milios J 1990. "Thick" cell membranes revealed by immunocytochemical staining: a clue to the diagnosis of mesothelioma. Diagnostic Cytopathology 6: 9-13.

•Van Der Kwast TH, Versnel MA, Delahaye M et al 1987. Expression of epithelial membrane antigen on malignant mesothelial cells. An immunocytochemical and immunoelectron microscopic study. Acta Cytologica 32: 169-174.

Bibliografía
Manual of diagnostic antibodies for immunohistology / Anthony S.-Y. Leong, Kumarasen Cooper, F. Joel W.-M. Leong.