Sources/Clones
Advanced Immunochemical (polyclonal), American Diagnostic (polyclonal), Axcel (24FN, 3E2) and Dako (1009).
Fixation/Preparation
Antibodies to thrombomodulin are applicable to formalin-fixed, paraffin-embedded tissue.
Background
Thrombomodulin (TM) is a transmembrane glycoprotein composed of 575 amino acids (molecular weight 75 kD) with natural anticoagulant properties (Wen et al, 1987). It is normally expressed by a restricted number of cells, such as endothelial and mesothelial cells (Marnyama et al, 1985). In addition, synovial lining and syncytiotrophoblasts of human placenta also express TM. Although TM contains six domains that are structurally similar to epidermal growth factor (EGF), there is no cross-reaction of anti-TM with EGF (Collins et al, 1992). The anticoagulant activity of TM results from the activation of protein C and the subsequent action on factors Va and VIIIa and from the binding of thrombin (Suzuki et al, 1987).
Applications
Several immunohistochemical endothelial markers are currently available (Suthipintawong et al, 1995) and thrombomodulin serves as another marker, staining blood and lymphatic channels and their corresponding tumors consistently. In a recent study, TM antibody stained 95% of benign lymphatic lesions (including lymphangioma and lymphangiectasia) (Appleton et al, 1996). In addition, TM demonstrated positivity in 100% benign vascular tumors (pyogenic granuloma and hemangioma) and 94% of malignant vascular tumors (Kaposi's sarcoma, angiosarcoma and epithelioid hemangioendothelioma). Hence, TM serves as a sensitive marker for lymphatic endothelial cells and their tumors. There has also been recent interest in the use of TM as an immunohistochemical marker for mesothelial cells and malignant mesotheliomas. The results have been rather variable with some studies claiming high specificity whilst others were less specific in distinguishing mesothelioma from adenocarcinoma. Table 1 illustrates the positivity rate for TM: Based on these data, it appears that TM cannot be totally depended upon for the purpose of distinction between mesothelioma and pulmonary adenocarcinoma.
Comments
Clearly, the major role of TM remains in the confirmation of lymphatic and vascular tumors, although some advocate the use of TM as a mesothelioma-binding antibody in the standard panel of antibodies used for the evaluation of malignant mesothelioma (Ordonez, 1997).
References
•Appleton MAC, Attanoos RL, Jasani B 1996. Thrombomodulin as a marker of vascular and lymphatic tumors. Histopathology 29: 153-157.
•Attanoos RL, Goddard H, Gibbs AR 1996. Mesothelioma-binding antibodies: thrombomodulin, OV632 and HBME-1 and their use in the diagnosis of malignant mesothelioma. Histopathology 29: 209-215.
•Brown RW, Clark GM, Tandon AK, Allred DC 1993. Multiple marker immunohistochemical phenotypes distinguishing malignant pleura mesothelioma from pulmonary adenocarcinoma. Human Pathology 24: 347-354.
•Collins CL, Ordonez NG, Schaefer R et al 1992. Thrombomodulin expression in malignant pleural mesothelioma and pulmonary adenocarcinoma. American Journal of Pathology 141: 827-833.
•Doglioni C, Dei Tos AP, Laurino L et al 1996. Calretinin: a novel immunocytochemical marker for mesothelioma. American Journal of Surgical Pathology 20: 1037-1046.
•Manuyama I, Bell C, Majerus P 1985. Thrombomodulin is found on endothelium of arteries, veins, capillaries, and lymphatics, and on syncytiotrophoblasts of human placenta. Journal of Cellular Biology 101: 363-371.
•Ordonez NG 1997. Value of thrombomodulin immunostaining in the diagnosis of mesothelioma. Histopathology 31: 25-30.
•Suthipintawong C, Leong AS-Y, Vinyuvat S 1995. A comparative study of immunomarkers for lymphangiomas and hemangiomas. Applied Immunohistochemistry 3: 239-244.
•Suzukli K, Kusumoto H, Deyashiki Y et al 1987. Structure and expression of human thrombomodulin, a thrombin receptor on endothelium acting as a cofactor for protein C activation. EMBO Journal 6: 1891-1897.
•Wen D, Dittman W, Ye R, Deaven L, Margerus P, Sadler J 1987. Human thrombomodulins: Complete cDNA sequence and chromosome localization of the gene. Biochemistry 26: 4350-4435.
Bibliografia
Manual of diagnostic antibodies for immunohistology / Anthony S.-Y. Leong, Kumarasen Cooper, F. Joel W.-M. Leong.
Advanced Immunochemical (polyclonal), American Diagnostic (polyclonal), Axcel (24FN, 3E2) and Dako (1009).
Fixation/Preparation
Antibodies to thrombomodulin are applicable to formalin-fixed, paraffin-embedded tissue.
Background
Thrombomodulin (TM) is a transmembrane glycoprotein composed of 575 amino acids (molecular weight 75 kD) with natural anticoagulant properties (Wen et al, 1987). It is normally expressed by a restricted number of cells, such as endothelial and mesothelial cells (Marnyama et al, 1985). In addition, synovial lining and syncytiotrophoblasts of human placenta also express TM. Although TM contains six domains that are structurally similar to epidermal growth factor (EGF), there is no cross-reaction of anti-TM with EGF (Collins et al, 1992). The anticoagulant activity of TM results from the activation of protein C and the subsequent action on factors Va and VIIIa and from the binding of thrombin (Suzuki et al, 1987).
Applications
Several immunohistochemical endothelial markers are currently available (Suthipintawong et al, 1995) and thrombomodulin serves as another marker, staining blood and lymphatic channels and their corresponding tumors consistently. In a recent study, TM antibody stained 95% of benign lymphatic lesions (including lymphangioma and lymphangiectasia) (Appleton et al, 1996). In addition, TM demonstrated positivity in 100% benign vascular tumors (pyogenic granuloma and hemangioma) and 94% of malignant vascular tumors (Kaposi's sarcoma, angiosarcoma and epithelioid hemangioendothelioma). Hence, TM serves as a sensitive marker for lymphatic endothelial cells and their tumors. There has also been recent interest in the use of TM as an immunohistochemical marker for mesothelial cells and malignant mesotheliomas. The results have been rather variable with some studies claiming high specificity whilst others were less specific in distinguishing mesothelioma from adenocarcinoma. Table 1 illustrates the positivity rate for TM: Based on these data, it appears that TM cannot be totally depended upon for the purpose of distinction between mesothelioma and pulmonary adenocarcinoma.
Comments
Clearly, the major role of TM remains in the confirmation of lymphatic and vascular tumors, although some advocate the use of TM as a mesothelioma-binding antibody in the standard panel of antibodies used for the evaluation of malignant mesothelioma (Ordonez, 1997).
References
•Appleton MAC, Attanoos RL, Jasani B 1996. Thrombomodulin as a marker of vascular and lymphatic tumors. Histopathology 29: 153-157.
•Attanoos RL, Goddard H, Gibbs AR 1996. Mesothelioma-binding antibodies: thrombomodulin, OV632 and HBME-1 and their use in the diagnosis of malignant mesothelioma. Histopathology 29: 209-215.
•Brown RW, Clark GM, Tandon AK, Allred DC 1993. Multiple marker immunohistochemical phenotypes distinguishing malignant pleura mesothelioma from pulmonary adenocarcinoma. Human Pathology 24: 347-354.
•Collins CL, Ordonez NG, Schaefer R et al 1992. Thrombomodulin expression in malignant pleural mesothelioma and pulmonary adenocarcinoma. American Journal of Pathology 141: 827-833.
•Doglioni C, Dei Tos AP, Laurino L et al 1996. Calretinin: a novel immunocytochemical marker for mesothelioma. American Journal of Surgical Pathology 20: 1037-1046.
•Manuyama I, Bell C, Majerus P 1985. Thrombomodulin is found on endothelium of arteries, veins, capillaries, and lymphatics, and on syncytiotrophoblasts of human placenta. Journal of Cellular Biology 101: 363-371.
•Ordonez NG 1997. Value of thrombomodulin immunostaining in the diagnosis of mesothelioma. Histopathology 31: 25-30.
•Suthipintawong C, Leong AS-Y, Vinyuvat S 1995. A comparative study of immunomarkers for lymphangiomas and hemangiomas. Applied Immunohistochemistry 3: 239-244.
•Suzukli K, Kusumoto H, Deyashiki Y et al 1987. Structure and expression of human thrombomodulin, a thrombin receptor on endothelium acting as a cofactor for protein C activation. EMBO Journal 6: 1891-1897.
•Wen D, Dittman W, Ye R, Deaven L, Margerus P, Sadler J 1987. Human thrombomodulins: Complete cDNA sequence and chromosome localization of the gene. Biochemistry 26: 4350-4435.
Bibliografia
Manual of diagnostic antibodies for immunohistology / Anthony S.-Y. Leong, Kumarasen Cooper, F. Joel W.-M. Leong.
