[Immunocytochemical localization of factor VIII-related antigen in blood vessels of the human central nervous system]

Abstract

Using both immunohistochemical and immunoelectron microscopic techniques with periodatelysine-paraformaldehyde (PLP) fixation, we have studied the distribution of Factor VIII-related antigen (F VIII R: Ag) in 14 cases of human central nervous system (CNS) tumors and 1 sample of non-tumor brain tissue. F VIII R: Ag was localized to the vascular lumen, to the intercellular spaces between endothelial cells (apparently without tight junctions), and to the endothelial cell basement membrane. In the cytoplasm, F VIII R: Ag was found in the endoplasmic reticulum, perinuclear space, and intracytoplasmic vacuoles and vesicles only. Characteristic of malignant tumors (6 out of 7) was strongly-positive dilated endoplasmic reticulum, whereas only 1 of 5 benign tumors showed such staining. This appears to reflect increased F VIII R: Ag synthesis in the malignant vessels. The non-tumor brain tissue showed normal capillary structure and very little F VIII R: Ag immunoreactivity. Six of 12 tumors and the non-tumor brain showed perinuclear F VIII R: Ag. Although the basement membranes were more irregular in the malignant tumors, staining was not grossly different from that of the more benign lesions. The finding of both ad-and ablumial vesicles containing F VIII R: Ag suggests that endocytosis, transcellular transport, and/or exocytosis, as well as F VIII R: Ag synthesis, occurs in the tumor endothelial cells. The relationship of these F VIII R: Ag abnormalities to the hypercoagulable state seen in some malignant brain tumor patients remains to be clarified.