Expression of epidermal growth-factor receptor in lymphangiomatosis: a new therapeutic target?

Abstract

Lymphangiomatosis is a rare disease characterised by multiple, infiltrative proliferations of lymphatic endothelium in the mediastinum and other somatic or visceral sites. Surgical resection, chemotherapy, and radiotherapy are all used to treat this disorder but have limited effectiveness. We have characterised the morphological and functional endothelial properties of the lymphatic tissue of one patient with mediastinal lymphangiomatosis and identified two morphologically and functionally different types of lymphatic endothelial cell (LECI and LECII). The morphology and cellular function of LECI cells resembled vascular endothelial cells and lymphatic tissues of healthy individuals (figure A; stained with an antibody against epidermal growth-factor [EGF] receptor). LECII cells, however, had increased proliferation and an altered immunohistochemical appearance—in particular, pronounced expression of CD31 and EGF-receptor (figure B; stained with an antibody against EGF-receptor). Increased expression of CD31 in LECII cells suggests they can be targeted with non-specific antiangiogenetic agents such as interferons or vascular endothelial growth-factor inhibitors. Furthermore, increased expression of EGF-receptors in LECII cells could provide a therapeutic target for selective EGF-receptor tyrosine-kinase inhibitors. These data show that mediastinal lymphangiomatosis is associated with an aberrant lymphatic endothelial cell-type that has targetable characteristics allowing for disease-specific pharmacological intervention.