Monoclonal Antibody D2-40, a New Marker of Lymphatic Endothelium, Reacts with Kaposi's Sarcoma and a Subset of Angiosarcomas

Abstract

There is controversy over the histogenesis of Kaposi's sarcoma (KS) from lymphatic or blood vessel endothelium. D2-40 is a novel monoclonal antibody to an Mr 40,000 O-linked sialoglycoprotein that reacts with a fixation-resistant epitope on lymphatic endothelium. We sought to establish the selectivity of D2-40 for lymphatic endothelium in normal tissues and compare its reactivity with the expression of the widely used vascular endothelial marker CD31 in a series of 62 formalin-fixed and paraffin-embedded vascular lesions including KS. In normal tissues, D2-40 stained the endothelium of lymphatic channels but not of blood vessels, including arteries and capillaries defined by reactivity with the blood vessel endothelial marker PAL-E. In our series of vascular lesions, D2-40 stained lymphangiomas (10/10), benign tumors of undisputed lymphatic origin, but not benign neoplasms or tumorlike lesions of blood vessel origin, including hemangiomas (0/10), glomus tumors (0/3), angiolipomas (0/2), pyogenic granulomas (0/2), vascular malformations (0/2), hemangiopericytoma (0/1), or hemangioendothelioma (0/1). D2-40 stained all cases of cutaneous KS (24/24) at all stages of progression, including patch, plaque, and nodular stages, supporting the concept that this disease originates from a cell type capable of undergoing lymphatic differentiation. D2-40 also stained three of seven angiosarcomas, indicating that a subset of these tumors can undergo at least partial differentiation along the lymphatic endothelial lineage and could be classified as lymphangiosarcomas. In comparison, CD31 was expressed in all benign and malignant vascular lesions, except for glomus tumors (0/3) and 5/10 lymphangiomas, in which staining was absent. We conclude that D2-40 is a new selective marker of lymphatic endothelium in normal tissues and vascular lesions and is valuable for studying benign and malignant vascular disorders in routinely processed tissue specimens.

Orbital lymphatics: do they exist?

“…In the last few years, however, a selective lymphatic marker has emerged to improve lymphatic identification significantly. 16 It is a monoclonal antibody, D 2-40, which reacts to an Mv 40 000 O-linked sialoglycoprotein on lymphatic endothelium. Additionally, it is suitable for fixed tissue specimens without epitope retrieval thus permitting far better preservation of cellular architecture.…”

D2-40 immunohistochemical analysis of pediatric vascular tumors reveals positivity in kaposiform hemangioendothelioma

“…5,19 D2-40, which also exhibits different reactivity in these two lesions, thus, can be used as an additional or alternative diagnostic marker. Kaposiform hemangioendothelioma is the fifth known vascular lesion that is reportedly positive for D2-40: previously the immunopositivity was shown in lymphatic malformation (lymphangioma), Kaposi sarcoma, angiosarcoma, 13 and hobnail hemangioma. 14 It has been suggested that D2-40 immunoreactivity in these neoplasms denotes a lymphothelial origin.…”

“…12 It has been observed that D2-40 selectively stains lymphatic endothelium in adult human tissue; this observation has been extended to finding D2-40 positivity in 'lymphangioma', Kaposi sarcoma and a subset of angiosarcoma, but not in benign tumors of blood vessels. 13 Recently, D2-40 immunopositivity was reported in hobnail hemangioma, suggesting that this tumor is of lymphatic origin. 14 Several studies employed D2-40 to evaluate lymphatics in nonvascular neoplastic and nonneoplastic lesions.…”

“…[15][16][17] Although the biologic significance of D2-40 immunoreactivity is unknown, it has been stated that the antibody reliably marks lymphatic but not blood vascular endothelium, [13][14][15][16][17] and postulated that staining of lesional cells in a vascular neoplasm denotes lymphothelial differentiation. 13,14 We immunostained kaposiform hemangioendotheliomas with D2-40 antibody to assess its diagnostic value and possibly elucidate the line of differentiation in this tumor. We also stained other pediatric vascular lesions to determine whether D2-40 would be helpful in differentiating kaposiform hemangioendothelioma, particularly from common infantile hemangioma and rapidly involuting and noninvoluting congenital hemangiomas, which can be difficult to histologically distinguish from kaposiform hemangioendothelioma in small biopsies.…”

D2-40 and calretinin—a tissue microarray analysis of 341 malignant mesotheliomas with emphasis on sarcomatoid differentiation

“…D2-40 is selective for lymphatic endothelia and has been shown to react with Kaposi's sarcoma, lymphangioma and Dabska tumor. 29,30 Membranous staining of D2-40 has been described in 51 of 53 (96%) 23 and 29 of 40 (72%) malignant mesotheliomas. 24 No single antibody has demonstrated entire sensitivity or specificity for malignant mesothelioma, 5,22,23,[31][32][33][34] and an exact description of expression frequency in areas with sarcomatoid differentiation in sarcomatoid malignant mesothelioma or biphasic malignant mesothelioma has been largely neglected.…”